{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:24:56Z","timestamp":1788305096346,"version":"build-2803163510"},"reference-count":289,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2013,4,26]],"date-time":"2013-04-26T00:00:00Z","timestamp":1366934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Ethanol-induced neuronal death during a sensitive period of brain development is considered one of the significant causes of fetal alcohol spectrum disorders (FASD). In rodent models, ethanol triggers robust apoptotic neurodegeneration during a period of active synaptogenesis that occurs around the first two postnatal weeks, equivalent to the third trimester in human fetuses. The ethanol-induced apoptosis is mitochondria-dependent, involving Bax and caspase-3 activation. Such apoptotic pathways are often mediated by sphingolipids, a class of bioactive lipids ubiquitously present in eukaryotic cellular membranes. While the central role of lipids in ethanol liver toxicity is well recognized, the involvement of sphingolipids in ethanol neurotoxicity is less explored despite mounting evidence of their importance in neuronal apoptosis. Nevertheless, recent studies indicate that ethanol-induced neuronal apoptosis in animal models of FASD is mediated or regulated by cellular sphingolipids, including via the pro-apoptotic action of ceramide and through the neuroprotective action of GM1 ganglioside. Such sphingolipid involvement in ethanol neurotoxicity in the developing brain may provide unique targets for therapeutic applications against FASD. Here we summarize findings describing the involvement of sphingolipids in ethanol-induced apoptosis and discuss the possibility that the combined action of various sphingolipids in mitochondria may control neuronal cell fate.<\/jats:p>","DOI":"10.3390\/brainsci3020670","type":"journal-article","created":{"date-parts":[[2013,4,26]],"date-time":"2013-04-26T11:27:28Z","timestamp":1366975648000},"page":"670-703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Involvement of Sphingolipids in Ethanol Neurotoxicity in the Developing Brain"],"prefix":"10.3390","volume":"3","author":[{"given":"Mariko","family":"Saito","sequence":"first","affiliation":[{"name":"Division of Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Orangeburg, NY 10962, USA"},{"name":"Department of Psychiatry, New York University Langone Medical Center, 550 First Ave.,  New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuo","family":"Saito","sequence":"additional","affiliation":[{"name":"Division of Analytical Psychopharmacology, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Orangeburg, NY 10962, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S91","DOI":"10.1194\/jlr.R800080-JLR200","article-title":"Bioactive sphingolipids: Metabolism and function","volume":"50","author":"Bartke","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/sj.embor.7400208","article-title":"The complex life of simple sphingolipids","volume":"5","author":"Futerman","year":"2004","journal-title":"EMBO Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4419-6741-1_1","article-title":"An overview of sphingolipid metabolism: From synthesis to breakdown","volume":"688","author":"Gault","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S1388-1981(02)00336-0","article-title":"Sphingosine in apoptosis signaling","volume":"1585","author":"Cuvillier","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/nrc1411","article-title":"Biologically active sphingolipids in cancer pathogenesis and treatment","volume":"4","author":"Ogretmen","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrm1103","article-title":"Sphingosine-1-phosphate: An enigmatic signalling lipid","volume":"4","author":"Spiegel","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.brainresrev.2008.10.001","article-title":"Regulation of ceramide-induced neuronal death: Cell metabolism meets neurodegeneration","volume":"59","author":"Arboleda","year":"2009","journal-title":"Brain Res. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.brainresrev.2004.07.014","article-title":"Sphingolipid metabolites in neural signalling and function","volume":"46","author":"Colombaioni","year":"2004","journal-title":"Brain Res. Brain Res. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/(SICI)1097-4547(20000415)60:2<141::AID-JNR2>3.0.CO;2-5","article-title":"Does ceramide play a role in neural cell apoptosis?","volume":"60","author":"Goswami","year":"2000","journal-title":"J. Neurosci. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.jns.2008.12.010","article-title":"Ceramide and neurodegeneration: Susceptibility of neurons and oligodendrocytes to cell damage and death","volume":"278","author":"Jana","year":"2009","journal-title":"J. Neurol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1016\/j.bbamem.2006.09.018","article-title":"Sphingolipids in apoptosis, survival and regeneration in the nervous system","volume":"1758","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.1017\/S1462399410001602","article-title":"Molecular insights into amyloid regulation by membrane cholesterol and sphingolipids: Common mechanisms in neurodegenerative diseases","volume":"12","author":"Fantini","year":"2010","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"44396","DOI":"10.1074\/jbc.M107239200","article-title":"Regulation of apoptosis during neuronal differentiation by ceramide and b-series complex gangliosides","volume":"276","author":"Bieberich","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4644","DOI":"10.1074\/jbc.M110.164392","article-title":"Developmentally regulated ceramide synthase 6 increases mitochondrial Ca2+ loading capacity and promotes apoptosis","volume":"286","author":"Novgorodov","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1194\/jlr.R003442","article-title":"Regulating survival and development in the retina: Key roles for simple sphingolipids","volume":"51","author":"Rotstein","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1523\/JNEUROSCI.17-09-02929.1997","article-title":"Distinct roles for ceramide and glucosylceramide at different stages of neuronal growth","volume":"17","author":"Schwarz","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/978-1-4614-0631-0_70","article-title":"Ceramide signaling in retinal degeneration","volume":"723","author":"Chen","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S231","DOI":"10.3233\/JAD-2012-111727","article-title":"Triangulated mal-signaling in Alzheimer\u2019s disease: Roles of neurotoxic ceramides, ER stress, and insulin resistance reviewed","volume":"30","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1007\/s11064-011-0692-y","article-title":"The roles of neutral sphingomyelinases in neurological pathologies","volume":"37","author":"Horres","year":"2012","journal-title":"Neurochem. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/j.1749-6632.1998.tb09679.x","article-title":"Promotion of neuronal survival by GM1 ganglioside. Phenomenology and mechanism of action","volume":"845","author":"Ferrari","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1007\/s11064-010-0286-0","article-title":"In search of a solution to the sphinx-like riddle of GM1","volume":"35","author":"Ledeen","year":"2010","journal-title":"Neurochem. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1007\/s00018-005-5188-y","article-title":"Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophins","volume":"62","author":"Mocchetti","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1007\/s11064-012-0764-7","article-title":"Essential roles of gangliosides in the formation and maintenance of membrane microdomains in brain tissues","volume":"37","author":"Ohmi","year":"2012","journal-title":"Neurochem. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0361-9230(90)90297-D","article-title":"The role(s) of gangliosides in neural differentiation and repair: A perspective","volume":"24","author":"Schengrund","year":"1990","journal-title":"Brain Res. Bull."},{"key":"ref_26","first-page":"S507","article-title":"Monosialogangliosides, neuroprotection, and neuronal repair processes","volume":"9","author":"Skaper","year":"1992","journal-title":"J. Neurotrauma"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.tox.2010.10.006","article-title":"Strategies for the early detection of drug-induced hepatic steatosis in preclinical drug safety evaluation studies","volume":"279","author":"Amacher","year":"2011","journal-title":"Toxicology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.alcohol.2004.07.008","article-title":"Alcoholic fatty liver: Its pathogenesis and mechanism of progression to inflammation and fibrosis","volume":"34","author":"Lieber","year":"2004","journal-title":"Alcohol"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E10","DOI":"10.1152\/ajpendo.00011.2008","article-title":"Alcohol and lipid metabolism","volume":"295","author":"Sozio","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Longato, L., Ripp, K., Setshedi, M., Dostalek, M., Akhlaghi, F., Branda, M., Wands, J.R., and  de la Monte, S.M. (2012). Insulin resistance, ceramide accumulation, and endoplasmic reticulum stress in human chronic alcohol-related liver disease. Oxid. Med. Cell. Longev., 2012.","DOI":"10.1155\/2012\/479348"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.trsl.2011.03.005","article-title":"Alcoholic-induced hepatic steatosis-role of ceramide and protein phosphatase 2A","volume":"158","author":"Supakul","year":"2011","journal-title":"Transl. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1093\/alcalc\/agn105","article-title":"Foetal Alcohol Spectrum Disorders and alterations in brain and behaviour","volume":"44","author":"Guerri","year":"2009","journal-title":"Alcohol Alcohol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1177\/15353702-0323006-06","article-title":"Animal model systems for the study of alcohol teratology","volume":"230","author":"Cudd","year":"2005","journal-title":"Exp. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1111\/j.1530-0277.1998.tb03653.x","article-title":"Neuroanatomical and neurophysiological mechanisms involved in central nervous system dysfunctions induced by prenatal alcohol exposure","volume":"22","author":"Guerri","year":"1998","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1126\/science.287.5455.1056","article-title":"Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome","volume":"287","author":"Ikonomidou","year":"2000","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0165-3806(02)00279-1","article-title":"Ethanol-induced apoptotic neurodegeneration in the developing C57BL\/6 mouse brain","volume":"133","author":"Olney","year":"2002","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.nbd.2010.05.025","article-title":"Alcohol-induced neuroapoptosis in the fetal macaque brain","volume":"40","author":"Farber","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1111\/j.1530-0277.2011.01549.x","article-title":"Local and regional network function in behaviorally relevant cortical circuits of adult mice following postnatal alcohol exposure","volume":"35","author":"Wilson","year":"2011","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1002\/jnr.21759","article-title":"C-jun N-terminal kinase regulates the interaction between 14-3-3 and Bad in ethanol-induced cell death","volume":"86","author":"Han","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/neu.20208","article-title":"Effect of bax deletion on ethanol sensitivity in the neonatal rat cerebellum","volume":"66","author":"Heaton","year":"2006","journal-title":"J. Neurobiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1093\/jnen\/64.6.490","article-title":"Molecular regulation of acute ethanol-induced neuron apoptosis","volume":"64","author":"Nowoslawski","year":"2005","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1038\/sj.cdd.4401277","article-title":"Ethanol-induced neuronal apoptosis in vivo requires BAX in the developing mouse brain","volume":"10","author":"Young","year":"2003","journal-title":"Cell Death Differ."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/j.1471-4159.2010.06913.x","article-title":"Involvement of ceramide in ethanol-induced apoptotic neurodegeneration in the neonatal mouse brain","volume":"115","author":"Saito","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1111\/j.1471-4159.2007.04836.x","article-title":"Ethanol alters lipid profiles and phosphorylation status of AMP-activated protein kinase in the neonatal mouse brain","volume":"103","author":"Saito","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1097\/01.alc.0000175011.22307.61","article-title":"Ethanol-induced changes in the content of triglycerides, ceramides, and glucosylceramides in cultured neurons","volume":"29","author":"Saito","year":"2005","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1093\/oxfordjournals.alcalc.a045164","article-title":"Changes in whole brain membranes of rats following pre- and post-natal exposure to ethanol","volume":"26","author":"Duffy","year":"1991","journal-title":"Alcohol Alcohol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.chemphyslip.2008.02.014","article-title":"Biochemical and biological functions of docosahexaenoic acid in the nervous system: Modulation by ethanol","volume":"153","author":"Kim","year":"2008","journal-title":"Chem. Phys. Lipids"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/BF02815010","article-title":"Effects of chronic ethanol exposure on cultured cerebellar granule cells","volume":"26","author":"Pitto","year":"1995","journal-title":"Mol. Chem. Neuropathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/j.1471-4159.2012.07710.x","article-title":"Elevation of GM2 ganglioside during ethanol-induced apoptotic neurodegeneration in the developing mouse brain","volume":"121","author":"Saito","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/jnr.10274","article-title":"Ethanol-induced increase of sphingosine recycling for ganglioside biosynthesis: A study performed on cerebellar granule cells in culture","volume":"69","author":"Ravasi","year":"2002","journal-title":"J. Neurosci. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/cne.903240408","article-title":"Early postnatal alcohol exposure acutely and permanently reduces the number of granule cells and mitral cells in the rat olfactory bulb: A stereological study","volume":"324","author":"Bonthius","year":"1992","journal-title":"Comp. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/S0006-8993(02)03561-8","article-title":"Neonatal ethanol produces cerebellar deep nuclear cell loss and correlated disruption of eyeblink conditioning in adult rats","volume":"956","author":"Green","year":"2002","journal-title":"Brain Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1111\/j.1530-0277.1995.tb01619.x","article-title":"Permanent neuronal cell loss in the inferior olive of adult rats exposed to alcohol during the brain growth spurt: A stereological investigation","volume":"19","author":"Napper","year":"1995","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/tera.1420400205","article-title":"Differential neuronal loss following early postnatal alcohol exposure","volume":"40","author":"Pierce","year":"1989","journal-title":"Teratology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0892-0362(97)00062-7","article-title":"Neonatal binge ethanol exposure using intubation: Timing and dose effects on place learning","volume":"19","author":"Goodlett","year":"1997","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1530-0277.2002.tb02435.x","article-title":"Selective and enduring deficits in spatial learning after limited neonatal binge alcohol exposure in male rats","volume":"26","author":"Johnson","year":"2002","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.ntt.2005.07.002","article-title":"Postnatal ethanol exposure disrupts signal detection in adult rats","volume":"27","author":"Woolfrey","year":"2005","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0165-3806(02)00610-7","article-title":"Effects of ethanol on neurotrophic factors, apoptosis-related proteins, endogenous antioxidants, and reactive oxygen species in neonatal striatum: Relationship to periods of vulnerability","volume":"140","author":"Heaton","year":"2003","journal-title":"Dev. Brain Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.devbrainres.2003.08.005","article-title":"Ethanol effects on neonatal rat cortex: Comparative analyses of neurotrophic factors, apoptosis-related proteins, and oxidative processes during vulnerable and resistant periods","volume":"145","author":"Heaton","year":"2003","journal-title":"Dev. Brain Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1111\/j.1530-0277.1999.tb04286.x","article-title":"Neonatal ethanol exposure alters bcl-2 family mRNA levels in the rat cerebellar vermis","volume":"23","author":"Moore","year":"1999","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.nbd.2005.12.015","article-title":"Neuroapoptosis in the infant mouse brain triggered by a transient small increase in blood alcohol concentration","volume":"22","author":"Young","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_62","first-page":"250","article-title":"Effects of ethanol exposure on spatial learning in mice during synaptogenesis","volume":"46","author":"Furumiya","year":"2011","journal-title":"Nihon Arukoru Yakubutsu Igakkai Zasshi"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e101","DOI":"10.1371\/journal.pmed.0030101","article-title":"Nicotinamide protects against ethanol-induced apoptotic neurodegeneration in the developing mouse brain","volume":"3","author":"Ieraci","year":"2006","journal-title":"PLoS Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.neuroscience.2011.12.059","article-title":"Lithium prevents long-term neural and behavioral pathology induced by early alcohol exposure","volume":"206","author":"Sadrian","year":"2012","journal-title":"Neuroscience"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.nbd.2004.08.006","article-title":"Apoptotic neurodegeneration induced by ethanol in neonatal mice is associated with profound learning\/memory deficits in juveniles followed by progressive functional recovery in adults","volume":"17","author":"Wozniak","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.devbrainres.2004.11.005","article-title":"Ethanol-induced neuroapoptosis in the developing rodent cerebellum and related brain stem structures","volume":"155","author":"Dikranian","year":"2005","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_67","first-page":"738","article-title":"Alcohol-induced Purkinje cell loss with a single binge exposure in neonatal rats: A stereological study of temporal windows of vulnerability","volume":"21","author":"Goodlett","year":"1997","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0741-8329(90)90070-S","article-title":"A single day of alcohol exposure during the brain growth spurt induces brain weight restriction and cerebellar Purkinje cell loss","volume":"7","author":"Goodlett","year":"1990","journal-title":"Alcohol"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1111\/j.1530-0277.2003.tb04402.x","article-title":"The role of neurotrophic factors, apoptosis-related proteins, and endogenous antioxidants in the differential temporal vulnerability of neonatal cerebellum to ethanol","volume":"27","author":"Heaton","year":"2003","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1002\/jnr.20591","article-title":"Functional mechanisms of apoptosis-related proteins in neonatal rat cerebellum are differentially influenced by ethanol at postnatal days 4 and 7","volume":"81","author":"Paiva","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s12311-010-0219-0","article-title":"Mechanisms of ethanol-induced death of cerebellar granule cells","volume":"11","author":"Luo","year":"2012","journal-title":"Cerebellum"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/jnr.10208","article-title":"Ethanol exposure enhances cell death in the developing cerebral cortex: Role of brain-derived neurotrophic factor and its signaling pathways","volume":"68","author":"Climent","year":"2002","journal-title":"J. Neurosci. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/BF02740616","article-title":"Alcohol, astroglia, and brain development","volume":"15","author":"Guerri","year":"1997","journal-title":"Mol. Neurobiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0165-3806(93)90162-4","article-title":"Transient cortical astrogliosis induced by alcohol exposure during the neonatal brain growth spurt in rats","volume":"72","author":"Goodlett","year":"1993","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s11064-009-0116-4","article-title":"Tau phosphorylation and cleavage in ethanol-induced neurodegeneration in the developing mouse brain","volume":"35","author":"Saito","year":"2010","journal-title":"Neurochem. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1124\/mol.105.017004","article-title":"Ethanol induces apoptotic death of developing beta-endorphin neurons via suppression of cyclic adenosine monophosphate production and activation of transforming growth factor-beta1-linked apoptotic signaling","volume":"69","author":"Chen","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1111\/j.1530-0277.2008.00769.x","article-title":"Ethanol-mediated DNA damage and PARP-1 apoptotic responses in cultured fetal cortical neurons","volume":"32","author":"Cherian","year":"2008","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"26697","DOI":"10.1016\/S0021-9258(18)47075-5","article-title":"Cyclic AMP and ethanol interact to control apoptosis and differentiation in hypothalamic beta-endorphin neurons","volume":"269","author":"De","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.devbrainres.2004.02.009","article-title":"The serotonin-1A agonist ipsapirone prevents ethanol-associated death of total rhombencephalic neurons and prevents the reduction of fetal serotonin neurons","volume":"150","author":"Druse","year":"2004","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/syn.20875","article-title":"Vitamin C protects against ethanol and PTZ-induced apoptotic neurodegeneration in prenatal rat hippocampal neurons","volume":"65","author":"Naseer","year":"2011","journal-title":"Synapse"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0006-8993(01)03224-3","article-title":"Ethanol-induced alterations of neurotrophin receptor expression on Purkinje cells in the neonatal rat cerebellum","volume":"924","author":"Light","year":"2002","journal-title":"Brain Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.bbrc.2008.01.004","article-title":"Lithium blocks ethanol-induced modulation of protein kinases in the developing brain","volume":"367","author":"Chakraborty","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.neulet.2005.12.065","article-title":"Suppression of survival kinases and activation of JNK mediate ethanol-induced cell death in the developing rat brain","volume":"398","author":"Han","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.nbd.2008.05.009","article-title":"Ethanol causes and lithium prevents neuroapoptosis and suppression of pERK in the infant mouse brain","volume":"31","author":"Young","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8455","DOI":"10.1073\/pnas.93.16.8455","article-title":"A molecular mechanism for the effect of lithium on development","volume":"93","author":"Klein","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.bbrc.2006.09.138","article-title":"Lithium protects ethanol-induced neuronal apoptosis","volume":"350","author":"Zhong","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_87","first-page":"41","article-title":"Lithium-mediated protection against ethanol neurotoxicity","volume":"4","author":"Luo","year":"2010","journal-title":"Front. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.brainres.2011.11.010","article-title":"Differential effects of ethanol on c-jun N-terminal kinase, 14-3-3 proteins, and Bax in postnatal day 4 and postnatal day 7 rat cerebellum","volume":"1432","author":"Heaton","year":"2012","journal-title":"Brain Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0304-3940(02)01123-0","article-title":"Ethanol-mediated generation of reactive oxygen species in developing rat cerebellum","volume":"334","author":"Heaton","year":"2002","journal-title":"Neurosci. Lett."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1002\/jnr.22689","article-title":"Cyanidin-3-glucoside ameliorates ethanol neurotoxicity in the developing brain","volume":"89","author":"Ke","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"ref_91","first-page":"512","article-title":"Amelioration of ethanol-induced neurotoxicity in the neonatal rat central nervous system by antioxidant therapy","volume":"24","author":"Heaton","year":"2000","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.ijdevneu.2004.04.005","article-title":"Vitamin E protects against alcohol-induced cell loss and oxidative stress in the neonatal rat hippocampus","volume":"22","author":"Marino","year":"2004","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e38075","DOI":"10.1371\/journal.pone.0038075","article-title":"Cdc42-dependent activation of NADPH oxidase is involved in ethanol-induced neuronal oxidative stress","volume":"7","author":"Wang","year":"2012","journal-title":"PLoS One"},{"key":"ref_94","first-page":"1574","article-title":"Ethanol induces endoplasmic reticulum stress in the developing brain","volume":"35","author":"Ke","year":"2011","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1111\/j.1530-0277.2011.01445.x","article-title":"Ethanol influences on Bax translocation, mitochondrial membrane potential, and reactive oxygen species generation are modulated by vitamin E and brain-derived neurotrophic factor","volume":"35","author":"Heaton","year":"2011","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1471-2202-13-11","article-title":"Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons","volume":"13","author":"Ullah","year":"2012","journal-title":"BMC Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1046\/j.1471-4159.1997.68020578.x","article-title":"Ethanol promotes apoptosis in cerebellar granule cells by inhibiting the trophic effect of NMDA","volume":"68","author":"Bhave","year":"1997","journal-title":"J. Neurochem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1046\/j.1471-4159.1998.71010196.x","article-title":"Ethanol induces apoptosis in cerebellar granule neurons by inhibiting insulin-like growth factor 1 signaling","volume":"71","author":"Zhang","year":"1998","journal-title":"J. Neurochem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1523\/JNEUROSCI.19-09-03277.1999","article-title":"Brain-derived neurotrophic factor mediates the anti-apoptotic effect of NMDA in cerebellar granule neurons: Signal transduction cascades and site of ethanol action","volume":"19","author":"Bhave","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/j.1749-6632.2003.tb07522.x","article-title":"N-methyl-d-aspartate and TrkB receptor activation in cerebellar granule cells: An in vitro model of preconditioning to stimulate intrinsic survival pathways in neurons","volume":"993","author":"Jiang","year":"2003","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1126\/science.7701324","article-title":"Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor","volume":"267","author":"Yao","year":"1995","journal-title":"Science"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.neuroscience.2010.01.057","article-title":"Mesenchymal stem cells inhibition of chronic ethanol-induced oxidative damage via upregulation of phosphatidylinositol-3-kinase\/Akt and modulation of extracellular signal-regulated kinase 1\/2 activation in PC12 cells and neurons","volume":"167","author":"Liu","year":"2010","journal-title":"Neuroscience"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1083\/jcb.151.3.483","article-title":"Akt regulates cell survival and apoptosis at a postmitochondrial level","volume":"151","author":"Zhou","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1002\/jnr.22098","article-title":"Overexpression of glycogen synthase kinase 3 beta sensitizes neuronal cells to ethanol toxicity","volume":"87","author":"Liu","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.ejphar.2004.07.115","article-title":"Glycogen synthase kinase-3 inhibitors prevent caspase-dependent apoptosis induced by ethanol in cultured rat cortical neurons","volume":"499","author":"Takadera","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0165-3806(99)00171-6","article-title":"Glial-derived neurotrophic factor (GDNF) prevents ethanol-induced apoptosis and JUN kinase phosphorylation","volume":"119","author":"McAlhany","year":"2000","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1046\/j.1471-4159.2003.02130.x","article-title":"Ceramide pathways modulate ethanol-induced cell death in astrocytes","volume":"87","author":"Pascual","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1750-3639.2004.tb00079.x","article-title":"Chronic ethanol treatment enhances inflammatory mediators and cell death in the brain and in astrocytes","volume":"14","author":"Blanco","year":"2004","journal-title":"Brain Pathol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.brainresbull.2006.08.014","article-title":"Glial-derived neurotrophic factor (GDNF) prevents ethanol (EtOH) induced B92 glial cell death by both PI3K\/AKT and MEK\/ERK signaling pathways","volume":"71","author":"Villegas","year":"2006","journal-title":"Brain Res. Bull."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.brainres.2008.02.018","article-title":"Antioxidants prevent ethanol-associated apoptosis in fetal rhombencephalic neurons","volume":"1204","author":"Antonio","year":"2008","journal-title":"Brain Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1016\/j.freeradbiomed.2008.08.030","article-title":"Mechanism of alcohol-induced oxidative stress and neuronal injury","volume":"45","author":"Haorah","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/jnr.10767","article-title":"Ethanol-induced oxidative stress precedes mitochondrially mediated apoptotic death of cultured fetal cortical neurons","volume":"74","author":"Ramachandran","year":"2003","journal-title":"J. Neurosci. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.brainres.2009.06.029","article-title":"Antioxidant neuroprotection against ethanol-induced apoptosis in HN2-5 cells","volume":"1285","author":"Sheth","year":"2009","journal-title":"Brain Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s00401-007-0199-4","article-title":"Chronic ethanol exposure causes mitochondria dysfunction and oxidative stress in immature central nervous system neurons","volume":"113","author":"Chu","year":"2007","journal-title":"Acta Neuropathol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1023\/A:1021968526696","article-title":"Ethanol-induced cell death by lipid peroxidation in PC12 cells","volume":"22","author":"Sun","year":"1997","journal-title":"Neurochem. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1002\/jnr.21562","article-title":"Glutathione content as a potential mediator of the vulnerability of cultured fetal cortical neurons to ethanol-induced apoptosis","volume":"86","author":"Maffi","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"27855","DOI":"10.1074\/jbc.R111.254359","article-title":"Many ceramides","volume":"286","author":"Hannun","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"25847","DOI":"10.1074\/jbc.R200008200","article-title":"The Ceramide-centric universe of lipid-mediated cell regulation: Stress encounters of the lipid kind","volume":"277","author":"Hannun","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S1043-6618(03)00049-5","article-title":"The roles of ceramide and complex sphingolipids in neuronal cell function","volume":"47","author":"Buccoliero","year":"2003","journal-title":"Pharmacol. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00018-012-1038-x","article-title":"Ceramide function in the brain: When a slight tilt is enough","volume":"70","author":"Mencarelli","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s12031-008-9111-5","article-title":"Interactions of PACAP and ceramides in the control of granule cell apoptosis during cerebellar development","volume":"36","author":"Aubert","year":"2008","journal-title":"J. Mol. Neurosci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1089\/neu.2000.17.891","article-title":"Role of ceramide in neuronal cell death and differentiation","volume":"17","author":"Toman","year":"2000","journal-title":"J. Neurotrauma"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/0092-8674(94)90275-5","article-title":"Functional dichotomy of neutral and acidic sphingomyelinases in tumor necrosis factor signaling","volume":"78","author":"Wiegmann","year":"1994","journal-title":"Cell"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"14134","DOI":"10.1074\/jbc.M109.076810","article-title":"Neurons and oligodendrocytes recycle sphingosine 1-phosphate to ceramide: Significance for apoptosis and multiple sclerosis","volume":"285","author":"Qin","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"41888","DOI":"10.1074\/jbc.M112.413500","article-title":"Ablation of neuronal ceramide synthase 1 in mice decreases ganglioside levels and expression of myelin-associated glycoprotein in oligodendrocytes","volume":"287","author":"Ginkel","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1042\/BJ20111626","article-title":"Ceramide synthases at the centre of sphingolipid metabolism and biology","volume":"441","author":"Mullen","year":"2012","journal-title":"Biochem. J."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"26509","DOI":"10.1074\/jbc.M801597200","article-title":"Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia\/reoxygenation-induced Bax redistribution to mitochondria in NT-2 cells","volume":"283","author":"Jin","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"25940","DOI":"10.1074\/jbc.M701812200","article-title":"JNK3 signaling pathway activates ceramide synthase leading to mitochondrial dysfunction","volume":"282","author":"Yu","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e280","DOI":"10.1038\/cddis.2012.17","article-title":"C16 ceramide is crucial for triacylglycerol-induced apoptosis in macrophages","volume":"3","author":"Aflaki","year":"2012","journal-title":"Cell Death Dis."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"13606","DOI":"10.1074\/jbc.M009517200","article-title":"Induction of apoptosis through B-cell receptor cross-linking occurs via de novo generated C16-ceramide and involves mitochondria","volume":"276","author":"Kroesen","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1189\/jlb.0806529","article-title":"De novo C16- and C24-ceramide generation contributes to spontaneous neutrophil apoptosis","volume":"81","author":"Seumois","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/glia.20626","article-title":"Long-chain ceramide is elevated in presenilin 1 (PS1M146V) mouse brain and induces apoptosis in pS1 astrocytes","volume":"56","author":"Wang","year":"2008","journal-title":"Glia"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.mcn.2005.02.009","article-title":"Ceramide induces neuronal apoptosis through mitogen-activated protein kinases and causes release of multiple mitochondrial proteins","volume":"29","author":"Stoica","year":"2005","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1046\/j.0953-816x.2001.01581.x","article-title":"Ceramide-induced apoptosis in cortical neurons is mediated by an increase in p38 phosphorylation and not by the decrease in ERK phosphorylation","volume":"13","author":"Willaime","year":"2001","journal-title":"Eur. J. Neurosci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.neuro.2010.08.001","article-title":"Differential regulation of AKT, MAPK, and GSK3\u03b2 during C2-ceramide induced neuronal death","volume":"31","author":"Arboleda","year":"2010","journal-title":"Neurotoxicology"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1002\/(SICI)1097-4547(19990915)57:6<884::AID-JNR14>3.0.CO;2-A","article-title":"Overexpression of Akt (protein kinase B) confers protection against apoptosis and prevents formation of ceramide in response to pro-apoptotic stimuli","volume":"57","author":"Goswami","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"15523","DOI":"10.1016\/S0021-9258(18)82288-8","article-title":"Ceramide activates heterotrimeric protein phosphatase 2A","volume":"268","author":"Dobrowsky","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1242\/jcs.03473","article-title":"GSK-3beta acts downstream of PP2A and the PI 3-kinase-Akt pathway, and upstream of caspase-2 in ceramide-induced mitochondrial apoptosis","volume":"120","author":"Lin","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1096\/fj.06-7859rev","article-title":"Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival","volume":"22","author":"Junttila","year":"2008","journal-title":"FASEB J."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/S0968-0004(99)01375-4","article-title":"Regulation of protein kinase cascades by protein phosphatase 2A","volume":"24","author":"Millward","year":"1999","journal-title":"Trends Biochem. Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0891-5849(01)00655-4","article-title":"Ceramide in apoptosis signaling: Relationship with oxidative stress","volume":"31","author":"Salvayre","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/j.freeradbiomed.2006.01.035","article-title":"Sphingolipid signaling and redox regulation","volume":"40","author":"Won","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/jnr.22748","article-title":"Neutral sphingomyelinase activation precedes NADPH oxidase dependent damage in neurons exposed to the proinflammatory cytokine tumor necrosis factor-\u03b1","volume":"90","author":"Barth","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1194\/jlr.R031278","article-title":"Sphingolipids: Regulators of crosstalk between apoptosis and autophagy","volume":"54","author":"Young","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.cell.2012.01.038","article-title":"Sphingolipid metabolism cooperates with BAK and BAX to promote the mitochondrial pathway of apoptosis","volume":"148","author":"Chipuk","year":"2012","journal-title":"Cell"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s10495-009-0449-0","article-title":"Ceramide and activated bax act synergistically to permeabilize the mitochondrial outer membrane","volume":"15","author":"Ganesan","year":"2010","journal-title":"Apoptosis"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"20804","DOI":"10.1074\/jbc.M410869200","article-title":"Acid sphingomyelinase is indispensable for UV light-induced Bax conformational change at the mitochondrial membrane","volume":"280","author":"Kashkar","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"e19783","DOI":"10.1371\/journal.pone.0019783","article-title":"Mitochondrial ceramide-rich macrodomains functionalize Bax upon irradiation","volume":"6","author":"Lee","year":"2011","journal-title":"PLoS One"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"e48571","DOI":"10.1371\/journal.pone.0048571","article-title":"Modulation of mitochondrial outer membrane permeabilization and apoptosis by ceramide metabolism","volume":"7","author":"Rego","year":"2012","journal-title":"PLoS One"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1471-4159.2008.05383.x","article-title":"Lipidomic analysis and electron transport chain activities in C57BL\/6J mouse brain mitochondria","volume":"106","author":"Kiebish","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"17993","DOI":"10.1074\/jbc.M110.102988","article-title":"Identification and characterization of murine mitochondria-associated neutral sphingomyelinase (MA-nSMase), the mammalian sphingomyelin phosphodiesterase 5","volume":"285","author":"Wu","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1042\/BJ20031819","article-title":"Subcellular compartmentalization of ceramide metabolism: MAM (mitochondria-associated membrane) and\/or mitochondria?","volume":"382","author":"Bionda","year":"2004","journal-title":"Biochem. J."},{"key":"ref_153","first-page":"347","article-title":"Ceramide and mitochondria in ischemic brain injury","volume":"2","author":"Novgorodov","year":"2011","journal-title":"Int. J. Biochem. Mol. Biol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1111\/j.1471-4159.2006.03977.x","article-title":"Ceramide is the key mediator of oxidative stress-induced apoptosis in retinal photoreceptor cells","volume":"98","author":"Sanvicens","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1523\/JNEUROSCI.5832-08.2009","article-title":"Developmental shift of cyclophilin D contribution to hypoxic-ischemic brain injury","volume":"29","author":"Wang","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1194\/jlr.M100442-JLR200","article-title":"Glucosylceramide synthesis and synthase expression protect against ceramide-induced stress","volume":"43","author":"Uchida","year":"2002","journal-title":"J. Lipid Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00232-001-0033-1","article-title":"The Involvement of sphingolipids in multidrug resistance","volume":"181","author":"Sietsma","year":"2001","journal-title":"J. Membr. Biol."},{"key":"ref_158","first-page":"40A","article-title":"Involvement of sphingomyelinase and the AKT-pathway in ethanol-induced neurodegeneration in the neonatal mouse brain","volume":"31","author":"Chakraborty","year":"2007","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_159","unstructured":"Saito, M., Chakraborty, G., Shah, R., Mao, R.F., and Saito, M. (2011). Unpublished work."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/alcalc\/ags106","article-title":"Insulin resistance, ceramide accumulation and endoplasmic reticulum stress in experimental chronic alcohol-induced steatohepatitis","volume":"48","author":"Ramirez","year":"2013","journal-title":"Alcohol Alcohol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.bbalip.2009.09.024","article-title":"Acyl-CoA synthesis, lipid metabolism and lipotoxicity","volume":"1801","author":"Li","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"G515","DOI":"10.1152\/ajpgi.00455.2011","article-title":"Imipramine blocks ethanol-induced ASMase activation, ceramide generation, and PP2A activation, and ameliorates hepatic steatosis in ethanol-fed mice","volume":"302","author":"Liangpunsakul","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"G1004","DOI":"10.1152\/ajpgi.00482.2009","article-title":"Inhibitory effect of ethanol on AMPK phosphorylation is mediated in part through elevated ceramide levels","volume":"298","author":"Liangpunsakul","year":"2010","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/cne.22018","article-title":"Binge-like postnatal alcohol exposure triggers cortical gliogenesis in adolescent rats","volume":"514","author":"Helfer","year":"2009","journal-title":"J. Comp. Neurol."},{"key":"ref_165","first-page":"678","article-title":"Resveratrol prevents alcohol-induced cognitive deficits and brain damage by blocking inflammatory signaling and cell death cascade in neonatal rat brain","volume":"117","author":"Tiwari","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1007\/s11064-007-9445-3","article-title":"Maternal alcohol consumption increases sphingosine levels in the brains of progeny mice","volume":"32","author":"Dasgupta","year":"2007","journal-title":"Neurochem. Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.1038\/cddis.2010.22","article-title":"Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development","volume":"1","author":"Wang","year":"2010","journal-title":"Cell Death Dis."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1471-2210-5-3","article-title":"Cross-talk between phosphatidic acid and ceramide during ethanol-induced apoptosis in astrocytes","volume":"5","author":"Schatter","year":"2005","journal-title":"BMC Pharmacol."},{"key":"ref_169","first-page":"44A","article-title":"Ceramide and GM2 increased in mitochondria in the developing brain exposed to ethanol","volume":"35","author":"Saito","year":"2011","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/neu.20208","article-title":"Ethanol influences on bax associations with mitochondrial membrane proteins in neonatal rat cerebellum","volume":"66","author":"Heaton","year":"2013","journal-title":"J. Neurobiol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"9441","DOI":"10.1523\/JNEUROSCI.3290-04.2004","article-title":"Pronounced cell death in the absence of NMDA receptors in the developing somatosensory thalamus","volume":"24","author":"Adams","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.bbr.2003.12.026","article-title":"Neurofunctional deficits and potentiated apoptosis by neonatal NMDA antagonist administration","volume":"153","author":"Fredriksson","year":"2004","journal-title":"Behav. Brain Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1126\/science.283.5398.70","article-title":"Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain","volume":"283","author":"Ikonomidou","year":"1999","journal-title":"Science"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1093\/toxsci\/kfj144","article-title":"Blockade of N-methyl-d-aspartate receptors by ketamine produces loss of postnatal day 3 monkey frontal cortical neurons in culture","volume":"91","author":"Wang","year":"2006","journal-title":"Toxicol. Sci."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1007\/s10495-007-0754-4","article-title":"Pathological apoptosis in the developing brain","volume":"12","author":"Blomgren","year":"2007","journal-title":"Apoptosis"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0197-0186(02)00046-3","article-title":"Ethanol sensitivity of NMDA receptors","volume":"41","author":"Allgaier","year":"2002","journal-title":"Neurochem. Int."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1196\/annals.1300.010","article-title":"NMDA receptor antagonism and the ethanol intoxication signal: From alcoholism risk to pharmacotherapy","volume":"1003","author":"Krystal","year":"2003","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/oxfordjournals.jbchem.a003067","article-title":"Alteration of apoptotic protease-activating factor-1 (APAF-1)-dependent apoptotic pathway during development of rat brain and liver","volume":"131","author":"Ota","year":"2002","journal-title":"J. Biochem."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1242\/dev.124.6.1239","article-title":"Bax promotes neuronal cell death and is downregulated during the development of the nervous system","volume":"124","author":"Vekrellis","year":"1997","journal-title":"Development"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1111\/j.1471-4159.2012.07723.x","article-title":"Ethanol triggers sphingosine 1-phosphate elevation along with neuroapoptosis in the developing mouse brain","volume":"121","author":"Chakraborty","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1007\/s11064-009-9975-y","article-title":"Developmental profiles of lipogenic enzymes and their regulators in the neonatal mouse brain","volume":"34","author":"Saito","year":"2009","journal-title":"Neurochem. Res."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.3390\/ijerph6072055","article-title":"The liver-brain axis of alcohol-mediated neurodegeneration: Role of toxic lipids","volume":"6","author":"Longato","year":"2009","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.cellsig.2008.07.011","article-title":"Sphingosine kinase\/sphingosine 1-phosphate signalling in central nervous system","volume":"21","author":"Okada","year":"2009","journal-title":"Cell Signal."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1002\/jnr.21586","article-title":"Multifaceted roles of sphingosine-1-phosphate: How does this bioactive sphingolipid fit with acute neurological injury?","volume":"86","author":"Singh","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1016\/j.bbamem.2006.10.018","article-title":"A house divided: Ceramide, sphingosine, and sphingosine-1-phosphate in programmed cell death","volume":"1758","author":"Taha","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.biochi.2010.02.008","article-title":"Sphingosine kinase: Role in regulation of bioactive sphingolipid mediators in inflammation","volume":"92","author":"Snider","year":"2010","journal-title":"Biochimie"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"37323","DOI":"10.1074\/jbc.M202798200","article-title":"Sphingosine 1-phosphate triggers both apoptotic and survival signals for human hepatic myofibroblasts","volume":"277","author":"Davaille","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.fertnstert.2012.06.008","article-title":"Sphingosine-1-phosphate inhibits H2O2-induced granulosa cell apoptosis via the PI3K\/Akt signaling pathway","volume":"98","author":"Nakahara","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.phrs.2009.12.005","article-title":"Dexamethasone protects human fibroblasts from apoptosis via an S1P3-receptor subtype dependent activation of PKB\/Akt and Bcl XL","volume":"61","author":"Nieuwenhuis","year":"2010","journal-title":"Pharmacol. Res."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"H3150","DOI":"10.1152\/ajpheart.00587.2006","article-title":"Signals from type 1 sphingosine 1-phosphate receptors enhance adult mouse cardiac myocyte survival during hypoxia","volume":"293","author":"Zhang","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"46832","DOI":"10.1074\/jbc.M306577200","article-title":"Sphingosine kinase 2 is a nuclear protein and inhibits DNA synthesis","volume":"278","author":"Igarashi","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"11346","DOI":"10.1074\/jbc.M807336200","article-title":"Subcellular origin of sphingosine 1-phosphate is essential for its toxic effect in lyase-deficient neurons","volume":"284","author":"Hagen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"40330","DOI":"10.1074\/jbc.M304455200","article-title":"Sphingosine kinase type 2 is a putative BH3-only protein that induces apoptosis","volume":"278","author":"Liu","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"37118","DOI":"10.1074\/jbc.M502207200","article-title":"SphK1 and SphK2, sphingosine kinase isoenzymes with opposing functions in sphingolipid metabolism","volume":"280","author":"Maceyka","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0306-4522(99)00288-2","article-title":"Sphingosine-1-phosphate induces apoptosis of cultured hippocampal neurons that requires protein phosphatases and activator protein-1 complexes","volume":"94","author":"Moore","year":"1999","journal-title":"Neuroscience"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.neulet.2009.12.070","article-title":"Involvement of mitochondria on neuroprotective effect of sphingosine-1-phosphate in cell death in an in vitro model of brain ischemia","volume":"470","author":"Miguel","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S0006-8993(98)01354-7","article-title":"Protective effects of the TNF-ceramide pathway against glutamate neurotoxicity on cultured mesencephalic neurons","volume":"819","author":"Shinpo","year":"1999","journal-title":"Brain Res."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.bbrc.2010.02.027","article-title":"Altered expression of sphingosine kinase 1 and sphingosine-1-phosphate receptor 1 in mouse hippocampus after kainic acid treatment","volume":"393","author":"Lee","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1042\/bj20020867","article-title":"Assessment of the role of sphingosine 1-phosphate and its receptors in high-density lipoprotein-induced stimulation of astroglial cell function","volume":"370","author":"Malchinkhuu","year":"2003","journal-title":"Biochem. J."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1046\/j.0953-816x.2001.01585.x","article-title":"Sphingosine-1-phosphate induces proliferation of astrocytes: Regulation by intracellular signalling cascades","volume":"13","author":"Toutant","year":"2001","journal-title":"Eur. J. Neurosci."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1124\/mol.64.5.1199","article-title":"Common signaling pathways link activation of murine PAR-1, LPA, and S1P receptors to proliferation of astrocytes","volume":"64","author":"Sorensen","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/glia.10180","article-title":"Sphingosine 1-phosphate induces the production of glial cell line-derived neurotrophic factor and cellular proliferation in astrocytes","volume":"41","author":"Yamagata","year":"2003","journal-title":"Glia"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.neuroscience.2009.12.020","article-title":"Sphingosine kinase 1 regulates the expression of proinflammatory cytokines and nitric oxide in activated microglia","volume":"166","author":"Nayak","year":"2010","journal-title":"Neuroscience"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1471-4159.2007.04755.x","article-title":"Distribution of sphingosine kinase activity and mRNA in rodent brain","volume":"103","author":"Blondeau","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"35257","DOI":"10.1074\/jbc.M203033200","article-title":"PKC-dependent activation of sphingosine kinase 1 and translocation to the plasma membrane. Extracellular release of sphingosine-1-phosphate induced by phorbol 12-myristate 13-acetate (PMA)","volume":"277","author":"Johnson","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1084\/jem.20040559","article-title":"Phosphorylation-dependent translocation of sphingosine kinase to the plasma membrane drives its oncogenic signalling","volume":"201","author":"Pitson","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1161\/STROKEAHA.109.568899","article-title":"Activation of sphingosine 1-phosphate receptor-1 by FTY720 is neuroprotective after ischemic stroke in rats","volume":"41","author":"Hasegawa","year":"2010","journal-title":"Stroke"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.bbrc.2011.08.070","article-title":"Activation of sphingosine kinase 2 is an endogenous protective mechanism in cerebral ischemia","volume":"413","author":"Pfeilschifter","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"3342","DOI":"10.1161\/STROKEAHA.109.560714","article-title":"Hypoxic preconditioning-induced cerebral ischemic tolerance: Role for microvascular sphingosine kinase 2","volume":"40","author":"Wacker","year":"2009","journal-title":"Stroke"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1161\/STROKEAHA.111.626911","article-title":"Sphingosine kinase 2 mediates cerebral preconditioning and protects the mouse brain against ischemic injury","volume":"43","author":"Yung","year":"2012","journal-title":"Stroke"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1096\/fj.10-167502","article-title":"Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration","volume":"25","author":"Strub","year":"2011","journal-title":"FASEB J."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1007\/s00395-011-0223-7","article-title":"A novel role for mitochondrial sphingosine-1-phosphate produced by sphingosine kinase-2 in PTP-mediated cell survival during cardioprotection","volume":"106","author":"Gomez","year":"2011","journal-title":"Basic Res. Cardiol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1002\/hep.21384","article-title":"Sphingosine 1-phosphate protects rat liver sinusoidal endothelial cells from ethanol-induced apoptosis: Role of intracellular calcium and nitric oxide","volume":"44","author":"Zheng","year":"2006","journal-title":"Hepatology"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"115","DOI":"10.4103\/0301-4738.94052","article-title":"Sphingosine-1 phosphate prevents ethanol-induced corneal epithelial apoptosis","volume":"60","author":"Fournie","year":"2012","journal-title":"Indian J. Ophthalmol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1006\/abbi.1999.1203","article-title":"Ethanol potentiates the mitogenic effects of sphingosine 1-phosphate by a zinc- and calcium-dependent mechanism in fibroblasts","volume":"366","author":"Huang","year":"1999","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_216","unstructured":"Saito, M., Chakraborty, G., Shah, R., and Saito, M. (2012). Unpublished work."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.pharmthera.2007.04.006","article-title":"Sphingosine 1-phosphate receptors in health and disease: Mechanistic insights from gene deletion studies and reverse pharmacology","volume":"115","author":"Brinkmann","year":"2007","journal-title":"Pharmacol. Ther."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.4161\/auto.21376","article-title":"Autophagy is a protective response to ethanol neurotoxicity","volume":"8","author":"Chen","year":"2012","journal-title":"Autophagy"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1111\/j.1530-0277.2007.00354.x","article-title":"Embryonic cerebral cortical progenitors are resistant to apoptosis, but increase expression of suicide receptor DISC-complex genes and suppress autophagy following ethanol exposure","volume":"31","author":"Prock","year":"2007","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1053\/j.gastro.2010.07.041","article-title":"Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice","volume":"139","author":"Ding","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"248","DOI":"10.4161\/auto.7.2.14347","article-title":"Selective taste of ethanol-induced autophagy for mitochondria and lipid droplets","volume":"7","author":"Ding","year":"2011","journal-title":"Autophagy"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1111\/j.1530-0277.2012.01742.x","article-title":"Autophagy in alcohol-induced liver diseases","volume":"36","author":"Dolganiuc","year":"2012","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_223","doi-asserted-by":"crossref","unstructured":"Lin, C.W., Zhang, H., Li, M., Xiong, X., Chen, X., Chen, X., Charlie Dong, X., and Yin, X.M. (2013). Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and  non-alcoholic fatty liver conditions in mice. J. Hepatol.","DOI":"10.1016\/j.jhep.2013.01.011"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"63","DOI":"10.4161\/auto.22490","article-title":"Multilevel regulation of autophagosome content by ethanol oxidation in HepG2 cells","volume":"9","author":"Thomes","year":"2013","journal-title":"Autophagy"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"45","DOI":"10.4161\/auto.3416","article-title":"Is autophagy the key mechanism by which the sphingolipid rheostat controls the cell fate decision?","volume":"3","author":"Lavieu","year":"2007","journal-title":"Autophagy"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cbpb.2012.05.006","article-title":"The control of the balance between ceramide and sphingosine-1-phosphate by sphingosine kinase: Oxidative stress and the seesaw of cell survival and death","volume":"163","author":"Williams","year":"2012","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"18384","DOI":"10.1074\/jbc.M313561200","article-title":"Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1","volume":"279","author":"Scarlatti","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"38568","DOI":"10.1074\/jbc.M110.170621","article-title":"Kdo2-lipid A, a TLR4-specific agonist, induces de novo sphingolipid biosynthesis in RAW264.7 macrophages, which is essential for induction of autophagy","volume":"285","author":"Sims","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.bbrc.2011.06.061","article-title":"Sphingolipid synthesis is involved in autophagy in Saccharomyces cerevisiae","volume":"410","author":"Yamagata","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"558","DOI":"10.4161\/auto.5.4.8390","article-title":"Ceramide-induced autophagy: To junk or to protect cells?","volume":"5","author":"Pattingre","year":"2009","journal-title":"Autophagy"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/nchembio.1059","article-title":"Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy","volume":"8","author":"Sentelle","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"39898","DOI":"10.1074\/jbc.M112.416552","article-title":"Regulation of autophagy and its associated cell death by \u201csphingolipid rheostat\u201d: Reciprocal role of ceramide and sphingosine 1-phosphate in the mammalian target of rapamycin pathway","volume":"87","author":"Taniguchi","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"8518","DOI":"10.1074\/jbc.M506182200","article-title":"Regulation of autophagy by sphingosine kinase 1 and its role in cell survival during nutrient starvation","volume":"281","author":"Lavieu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1023\/A:1020224016830","article-title":"Ganglioside function in calcium homeostasis and signaling","volume":"27","author":"Ledeen","year":"2002","journal-title":"Neurochem. Res."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1097\/00062752-200301000-00004","article-title":"Structure, organization, and function of glycosphingolipids in membrane","volume":"10","author":"Hakomori","year":"2003","journal-title":"Curr. Opin. Hematol."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"537","DOI":"10.5650\/jos.60.537","article-title":"Structures, biosynthesis, and functions of gangliosides\u2014an overview","volume":"60","author":"Yu","year":"2011","journal-title":"J. Oleo Sci."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.neuroscience.2004.04.038","article-title":"Activation of Fas receptor is required for the increased formation of the disialoganglioside GD3 in cultured cerebellar granule cells committed to apoptotic death","volume":"126","author":"Castiglione","year":"2004","journal-title":"Neuroscience"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1523\/JNEUROSCI.22-10-03963.2002","article-title":"Beta-Amyloid-induced synthesis of the ganglioside GD3 is a requisite for cell cycle reactivation and apoptosis in neurons","volume":"22","author":"Copani","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.febslet.2006.12.046","article-title":"Role of Neu4L sialidase and its substrate ganglioside GD3 in neuronal apoptosis induced by catechol metabolites","volume":"581","author":"Hasegawa","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1093\/jnci\/djh254","article-title":"Gangliosides link the acidic sphingomyelinase mediated induction of ceramide to 12-lipoxygenase dependent apoptosis of neuroblastoma in response to fenretinide","volume":"96","author":"Lovat","year":"2004","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/sj.cdd.4401020","article-title":"An early increase in the disialoganglioside GD3 contributes to the development of neuronal apoptosis in culture","volume":"9","author":"Melchiorri","year":"2002","journal-title":"Cell Death Differ."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1126\/science.277.5332.1652","article-title":"Requirement for GD3 ganglioside in CD95- and ceramide-induced apoptosis","volume":"277","author":"Lenti","year":"1997","journal-title":"Science"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s10495-007-0757-1","article-title":"Dynamics of lipid raft components during lymphocyte apoptosis: The paradigmatic role of GD3","volume":"12","author":"Malorni","year":"2007","journal-title":"Apoptosis"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"376","DOI":"10.2174\/187152012800228670","article-title":"Ganglioside GD3 as a raft component in cell death regulation","volume":"12","author":"Sorice","year":"2012","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_245","first-page":"229","article-title":"Alterations in brain gangliosides and other lipids with Creutzfeldt-Jakob disease and subacute sclerosing panencephalitis (SSPE)","volume":"54","author":"Ando","year":"1984","journal-title":"Jpn. J. Exp. Med."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1006\/neur.1996.0045","article-title":"Ganglioside alterations in the central and peripheral nervous systems of patients with Creutzfeldt-Jakob disease","volume":"5","author":"Ohtani","year":"1996","journal-title":"Neurodegeneration"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1471-4159.1974.tb06931.x","article-title":"Ganglioside abnormalities in multiple sclerosis","volume":"23","author":"Yu","year":"1974","journal-title":"J. Neurochem."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S1388-1981(02)00339-6","article-title":"GD3 ganglioside and apoptosis","volume":"1585","author":"Malisan","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.3346\/jkms.2010.25.10.1492","article-title":"GD3 accumulation in cell surface lipid rafts prior to mitochondrial targeting contributes to amyloid-\u03b2-induced apoptosis","volume":"25","author":"Kim","year":"2010","journal-title":"J. Korean Med. Sci."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1096\/fj.99-1028com","article-title":"GD3 ganglioside directly targets mitochondria in a bcl-2-controlled fashion","volume":"14","author":"Rippo","year":"2000","journal-title":"FASEB J."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"36443","DOI":"10.1074\/jbc.M206021200","article-title":"Trafficking of ganglioside GD3 to mitochondria by tumor necrosis factor-alpha","volume":"277","author":"Colell","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.bbrc.2007.12.196","article-title":"GD3 nuclear localization after apoptosis induction in HUT-78 cells","volume":"368","author":"Tempera","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1006\/exnr.2000.7602","article-title":"Selective cell-cycle arrest and induction of apoptosis in proliferating neural cells by ganglioside GM3","volume":"168","author":"Nakatsuji","year":"2001","journal-title":"Exp. Neurol."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"3074","DOI":"10.1074\/jbc.270.7.3074","article-title":"Prevention of apoptotic neuronal death by GM1 ganglioside. Involvement of Trk neurotrophin receptors","volume":"270","author":"Ferrari","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1073\/pnas.92.11.5087","article-title":"Ganglioside GM1 binds to the Trk protein and regulates receptor function","volume":"92","author":"Mutoh","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1046\/j.1471-4159.2002.00831.x","article-title":"GM1 ganglioside induces phosphorylation and activation of Trk and Erk in brain","volume":"81","author":"Duchemin","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"49466","DOI":"10.1074\/jbc.M203240200","article-title":"Gangliosides activate Trk receptors by inducing the release of neurotrophins","volume":"277","author":"Rabin","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.neuropharm.2010.10.012","article-title":"Exogenous gangliosides increase the release of brain-derived neurotrophic factor","volume":"60","author":"Lim","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1111\/j.1471-4159.2007.05088.x","article-title":"GM1-induced activation of phosphatidylinositol 3-kinase: Involvement of Trk receptors","volume":"104","author":"Duchemin","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1083\/jcb.200404106","article-title":"BDNF-induced recruitment of TrkB receptor into neuronal lipid rafts: Roles in synaptic modulation","volume":"167","author":"Suzuki","year":"2004","journal-title":"J. Cell Biol."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"3554","DOI":"10.1074\/jbc.272.6.3554","article-title":"Tyrosine kinase receptors concentrated in caveolae-like domains from neuronal plasma membrane","volume":"272","author":"Wu","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0074-7742(09)85022-8","article-title":"Neurotrophic and neuroprotective actions of an enhancer of ganglioside biosynthesis","volume":"85","author":"Inokuchi","year":"2009","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"11014","DOI":"10.1523\/JNEUROSCI.3635-05.2005","article-title":"Enhanced susceptibility to kainate-induced seizures, neuronal apoptosis, and death in mice lacking gangliotetraose gangliosides: Protection with LIGA 20, a membrane-permeant analog of GM1","volume":"25","author":"Wu","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1007\/s11064-011-0437-y","article-title":"Mice lacking major brain gangliosides develop Parkinsonism","volume":"36","author":"Wu","year":"2011","journal-title":"Neurochem. Res."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1002\/jnr.23090","article-title":"Deficiency of ganglioside GM1 correlates with Parkinson\u2019s disease in mice and humans","volume":"90","author":"Wu","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"4072","DOI":"10.1523\/JNEUROSCI.6348-09.2010","article-title":"Impaired ganglioside metabolism in Huntington\u2019s disease and neuroprotective role of GM1","volume":"30","author":"Maglione","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1159\/000063604","article-title":"Alzheimer disease-effect of continuous intracerebroventricular treatment with GM1 ganglioside and a systematic activation programme","volume":"14","author":"Svennerholm","year":"2002","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.jns.2012.10.024","article-title":"A randomized, controlled, delayed start trial of GM1 ganglioside in treated Parkinson\u2019s disease patients","volume":"324","author":"Schneider","year":"2013","journal-title":"J. Neurol. Sci."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1212\/WNL.50.6.1630","article-title":"Parkinson\u2019s disease: Improved function with GM1 ganglioside treatment in a randomized placebo-controlled study","volume":"50","author":"Schneider","year":"1998","journal-title":"Neurology"},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jns.2010.02.009","article-title":"GM1 ganglioside in Parkinson\u2019s disease: Results of a five year open study","volume":"292","author":"Schneider","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/S0196-0644(05)82748-9","article-title":"Past and current clinical studies with GM-1 ganglioside in acute spinal cord injury","volume":"22","author":"Geisler","year":"1993","journal-title":"Ann. Emerg. Med."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1161\/01.STR.25.8.1552","article-title":"Early treatment of stroke with monosialoganglioside GM1. Efficacy and safety results of the early stroke trial","volume":"25","author":"Lenzi","year":"1994","journal-title":"Stroke"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0741-8329(94)90096-5","article-title":"Chronic ethanol effects on glycoconjugates and glycosyltransferases of rat brain","volume":"11","author":"Palestini","year":"1994","journal-title":"Alcohol"},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0741-8329(95)02059-4","article-title":"Ganglioside long-chain base composition of rat brain subcellular fractions after chronic ethanol administration","volume":"13","author":"Gornati","year":"1996","journal-title":"Alcohol"},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0005-2736(00)00210-8","article-title":"Ganglioside molecular species containing C18- and C20-sphingosine in mammalian nervous tissues and neuronal cell cultures","volume":"1469","author":"Sonnino","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1111\/j.1530-0277.1998.tb03902.x","article-title":"Long-term ethanol consumption selectively impairs ganglioside pathway in rat brain","volume":"22","author":"Ghosh","year":"1998","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.neuint.2005.07.005","article-title":"Effects of chronic ethanol administration on the activities and relative synthetic rates of myelin and synaptosomal plasma membrane-associated sialidase in the rat brain","volume":"48","author":"Azuine","year":"2006","journal-title":"Neurochem. Int."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.neuint.2006.02.001","article-title":"Chronic ethanol consumption down-regulates CMP-NeuAc:GM3 alpha2,8-sialyltransferase (ST8Sia-1) gene in the rat brain","volume":"49","author":"Garige","year":"2006","journal-title":"Neurochem. Int."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1111\/j.1530-0277.1994.tb00113.x","article-title":"Ganglioside GM1 reduces fetal alcohol effects in rat pups exposed to ethanol in utero","volume":"18","author":"Hungund","year":"1994","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1007\/BF02536148","article-title":"Effect of prenatal and postnatal exposure to ethanol on rat central nervous system gangliosides and glycosidases","volume":"27","author":"Prasad","year":"1992","journal-title":"Lipids"},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1530-0277.1985.tb05598.x","article-title":"Gangliosides in axolemmal and synaptic membrane fractions from developing rats: Effects of maternal ethanol consumption on offspring","volume":"9","author":"Noronha","year":"1985","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0741-8329(99)00058-0","article-title":"Differential sensitivity of mouse neural crest cells to ethanol-induced toxicity","volume":"20","author":"Chen","year":"2000","journal-title":"Alcohol"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/S0741-8329(96)00073-0","article-title":"The membrane disordering effect of ethanol on neural crest cells in vitro and the protective role of GM1 ganglioside","volume":"13","author":"Chen","year":"1996","journal-title":"Alcohol"},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/0006-8993(94)90497-9","article-title":"Ethanol neurotoxicity in vitro: Effects of GM1 ganglioside and protein synthesis inhibition","volume":"654","author":"Heaton","year":"1994","journal-title":"Brain Res."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1023\/A:1020704218574","article-title":"Gangliosides attenuate ethanol-induced apoptosis in rat cerebellar granule neurons","volume":"24","author":"Saito","year":"1999","journal-title":"Neurochem. Res."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/j.1530-0277.1993.tb00771.x","article-title":"Role of gangliosides in behavioral and biochemical actions of alcohol: Cell membrane structure and function","volume":"17","author":"Hungund","year":"1993","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1016\/0006-2952(94)90511-8","article-title":"Reduction of fatty acid ethyl ester accumulation by ganglioside GM1 in rat fetus exposed to ethanol","volume":"48","author":"Hungund","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/0197-0186(94)90138-4","article-title":"Ganglioside GM1 reduces ethanol induced phospholipase A2 activity in synaptosomal preparations from mice","volume":"25","author":"Hungund","year":"1994","journal-title":"Neurochem. Int."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1111\/j.1530-0277.2007.00351.x","article-title":"Effects of gangliosides on ethanol-induced neurodegeneration in the developing mouse brain","volume":"31","author":"Saito","year":"2007","journal-title":"Alcohol. Clin. Exp. Res."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/3\/2\/670\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:46:24Z","timestamp":1760219184000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/3\/2\/670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,26]]},"references-count":289,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2013,6]]}},"alternative-id":["brainsci3020670"],"URL":"https:\/\/doi.org\/10.3390\/brainsci3020670","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,26]]}}}