{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:34:58Z","timestamp":1791513298418,"version":"4.3.4"},"reference-count":104,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Ethanol consumption remains a major concern at a world scale in terms of transient or irreversible neurological consequences, with motor, cognitive, or social consequences. Cerebellum is particularly vulnerable to ethanol, both during development and at the adult stage. In adults, chronic alcoholism elicits, in particular, cerebellar vermis atrophy, the anterior lobe of the cerebellum being highly vulnerable. Alcohol-dependent patients develop gait ataxia and lower limb postural tremor. Prenatal exposure to ethanol causes fetal alcohol spectrum disorder (FASD), characterized by permanent congenital disabilities in both motor and cognitive domains, including deficits in general intelligence, attention, executive function, language, memory, visual perception, and communication\/social skills. Children with FASD show volume deficits in the anterior lobules related to sensorimotor functions (Lobules I, II, IV, V, and VI), and lobules related to cognitive functions (Crus II and Lobule VIIB). Various mechanisms underlie ethanol-induced cell death, with oxidative stress and endoplasmic reticulum (ER) stress being the main pro-apoptotic mechanisms in alcohol abuse and FASD. Oxidative and ER stresses are induced by thiamine deficiency, especially in alcohol abuse, and are exacerbated by neuroinflammation, particularly in fetal ethanol exposure. Furthermore, exposure to ethanol during the prenatal period interferes with neurotransmission, neurotrophic factors and retinoic acid-mediated signaling, and reduces the number of microglia, which diminishes expected cerebellar development. We highlight the spectrum of cerebellar damage induced by ethanol, emphasizing physiological-based clinical profiles and biological mechanisms leading to cell death and disorganized development.<\/jats:p>","DOI":"10.3390\/ijerph18168678","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T21:27:40Z","timestamp":1629235660000},"page":"8678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Mechanisms of Ethanol-Induced Cerebellar Ataxia: Underpinnings of Neuronal Death in the Cerebellum"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0513-1811","authenticated-orcid":false,"given":"Hiroshi","family":"Mitoma","sequence":"first","affiliation":[{"name":"Medical Education Promotion Center, Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Manto","sequence":"additional","affiliation":[{"name":"Unit\u00e9 des Ataxies C\u00e9r\u00e9belleuses, Service de Neurologie, CHU-Charleroi, 6000 Charleroi, Belgium"},{"name":"Service des Neurosciences, University of Mons, 7000 Mons, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aasef G.","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland VA Medical Center, University Hospitals Cleveland Medical Center, Cleveland, OH 44022, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Manto, M.U., and Pandolfo, M. (2002). Alcohol toxicity in the cerebellum: Clinical aspects. The Cerebellum and Its Disorders, Cambridge University Press.","DOI":"10.1017\/CBO9780511666469"},{"key":"ref_2","unstructured":"Subramony, S.H., and D\u00fcrr, A. (2012). Nutritional cerebellar degeneration, with comments on its relationship to Wernicke disease and alcoholism. Handbook of Clinical Neurology. Vol. 103 (3rd Series) Ataxic Disorders, Elsevier."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s12311-014-0638-4","article-title":"Ethanol-induced cerebellar ataxia: Cellular and molecular mechanisms","volume":"14","author":"Dar","year":"2015","journal-title":"Cerebellum"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/B978-0-444-64189-2.00022-6","article-title":"Toxic-induced cerebellar syndrome: From the fetal to the elderly","volume":"155","author":"Manto","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"ref_5","first-page":"271","article-title":"Nutritional cerebellar degeneration","volume":"Volume 28","author":"Vinken","year":"1976","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_6","unstructured":"Victor, M., Adams, R.D., and Collins, G.H. (1989). The Wernicke-Korsakoff Syndrome and Related Neurological Disorders due to Alcoholism and Malnutrition, FA Davis. [2nd ed.]."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s12311-015-0674-8","article-title":"Effects of ethanol on the cerebellum: Advances and prospects","volume":"14","author":"Luo","year":"2015","journal-title":"Cerebellum"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/ddrr.72","article-title":"Neuroimaging and fetal alcohol spectrum disorders","volume":"15","author":"Norman","year":"2009","journal-title":"Dev. Disabil. Res. Rev."},{"key":"ref_9","first-page":"199","article-title":"Acute and long-term changes in the cerebellum following developmental exposure to ethanol","volume":"2","author":"West","year":"1993","journal-title":"Alcohol Alcohol. Suppl."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/978-3-319-98788-0_14","article-title":"Engineered Animal Models Designed for Investigating Ethanol Metabolism, Toxicity and Cancer","volume":"1032","author":"Marshall","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104584","DOI":"10.1016\/j.neuint.2019.104584","article-title":"Neurochemical mechanisms underlying acute and chronic ethanol-mediated responses in zebrafish: The role of mitochondrial bioenergetics","volume":"131","author":"Nunes","year":"2019","journal-title":"Neurochem. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.4161\/15548627.2014.981916","article-title":"Autophagy and ethanol neurotoxicity","volume":"10","author":"Luo","year":"2014","journal-title":"Autophagy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.ejim.2007.06.033","article-title":"Alcoholism Treatment Study Group. Acute alcohol intocication","volume":"19","author":"Vonghia","year":"2008","journal-title":"Eur. J. Intern. Med."},{"key":"ref_14","unstructured":"Ito, M. (1984). The Cerebellum and Neural Control, Raven Press."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1038\/nn.3559","article-title":"Opposite actions of alcohol on tonic GABA (A) receptor currents mediated by nNOS and PKC activity","volume":"16","author":"Kaplan","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1007\/s12311-014-0639-3","article-title":"Mini-Review: Effects of ethanol on GABAA receptor-mediated neurotransmission in cerebellar cortex\u2014Recent advances","volume":"14","author":"Valenzuela","year":"2015","journal-title":"Cerebellum"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1523\/JNEUROSCI.06-07-01952.1986","article-title":"Adenosine contain in neurons in the brain localized by immunocytochemistry","volume":"6","author":"Braas","year":"1986","journal-title":"J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5693","DOI":"10.1523\/JNEUROSCI.15-08-05693.1995","article-title":"Pre- and postsynaptic determinants of EPSC waveform at cerebellar climbing fiber and parallel fiber to Purkinje cell synapses","volume":"15","author":"Takahashi","year":"1995","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1523\/JNEUROSCI.16-05-01623.1996","article-title":"Contributions of calcium-dependent and calcium-independent mechanisms to presynaptic inhibition at a cerebellar synapse","volume":"16","author":"Dittman","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_20","first-page":"537","article-title":"Extracellular adenosine concentrations in hippocampal brain slices and the tonic inhibitory modulation of evoked excitatory responses","volume":"268","author":"Dunwiddie","year":"1994","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_21","unstructured":"Okada, Y. (1997). Cyclic AMP-dependent and independent mechanisms for presynaptic modulation of GABAergic transmission in the cerebellar cortex. Adenosine, Elsevier."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.1523\/JNEUROSCI.06-09-02707.1986","article-title":"Distribution of adenosine deaminase activity in rat brain and spinal cord","volume":"6","author":"Geiger","year":"1986","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/S1357-4310(99)01459-8","article-title":"Nucleoside transporters: Molecular biology and implications for therapeutic development","volume":"5","author":"Baldwin","year":"1999","journal-title":"Mol. Med. Today"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/nn1288","article-title":"The type 1 equilibrative nucleoside transporter regulates ethanol intoxication and preference","volume":"7","author":"Choi","year":"2004","journal-title":"Nat. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1016\/S0021-9258(19)39923-5","article-title":"Ethanol increases extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter","volume":"265","author":"Nagy","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1523\/JNEUROSCI.4430-05.2006","article-title":"Alcohol potently modulates climbing fiber \u2192 Purkinje neuron synapses: Role of metabotropic glutamate receptors","volume":"26","author":"Carta","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1002\/ana.410280608","article-title":"Cerebellar and frontal hypometabolism in alcoholic cerebelalr degeneration studied with positron emission tomography","volume":"28","author":"Gilman","year":"1990","journal-title":"Ann. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF00344826","article-title":"Computed tomography in alcoholic cerebellar atrophy","volume":"18","author":"Haubek","year":"1979","journal-title":"Neuroradiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1001\/archneur.1959.03840060001001","article-title":"A restricted form of cerebellar cortical degeneration occurring in alcoholic patients: Cerebellar cortical degenerations","volume":"1","author":"Victor","year":"1959","journal-title":"Arch. Neurol."},{"key":"ref_30","first-page":"436","article-title":"Impaired upper limb coordination in alcoholic cerebellar degeneration","volume":"54","author":"Adams","year":"1997","journal-title":"Ann. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0022-510X(82)90145-9","article-title":"Brain lesions in alcoholics. A neuropathological study with clinical correlations","volume":"56","author":"Torvik","year":"1982","journal-title":"J. Neurol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.0954-6820.1987.tb13041.x","article-title":"Brain lesions in alcoholics: Neuropathological observations","volume":"717","author":"Torvik","year":"1987","journal-title":"Acta. Med. Scand."},{"key":"ref_33","unstructured":"Lechtenberg, R. (1993). Effects of alcohol. Handbook of Cerebellar Diseases, Marcel Dekker."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1097\/00005072-199802000-00001","article-title":"The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain?","volume":"57","author":"Happer","year":"1998","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_35","first-page":"148","article-title":"Die Alkoholenzephalopathien im Obdvktionsgut","volume":"137","author":"Riethdorf","year":"1991","journal-title":"Zentralbl. Pathol."},{"key":"ref_36","first-page":"603","article-title":"Neurologic complication of alcohol abuse: Epidemiologic aspects","volume":"19","author":"Victor","year":"1978","journal-title":"Adv. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0022-510X(86)90049-3","article-title":"The prevalence of alcoholic cerebellar atrophy. A morphometric and histological study of an autopsy material","volume":"75","author":"Torvik","year":"1986","journal-title":"J. Neurol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/09595239000185071","article-title":"The contribution of Wernicke\u2019s disease encephalopathy to alcohol-related cerebellar damage","volume":"9","author":"Phillips","year":"1990","journal-title":"Drug Alcohol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1093\/qjmed\/93.7.449","article-title":"High ethanol intake and malnutrition in alcoholic cerebellar shrinkage","volume":"93","author":"Robert","year":"2000","journal-title":"QJM"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/S1474-4422(07)70104-7","article-title":"Wernicke\u2019s encephalopathy: New clinical settings and recent advances in diagnosis and management","volume":"6","author":"Sechi","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0306-4522(98)90664-9","article-title":"Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke\u2019s encephalopathy","volume":"91","author":"Baker","year":"1999","journal-title":"Neuroscience"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s00401-013-1233-3","article-title":"Human alcohol-related neuropathology","volume":"127","author":"Suzanne","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_43","first-page":"555","article-title":"Nutrition and alcohol neurotoxicity","volume":"15","author":"Manzo","year":"1994","journal-title":"Neurotoxicology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1023\/A:1020657129593","article-title":"Mechanisms of neuronal death in Wernicke\u2019s encephalopathy","volume":"13","author":"Hazell","year":"1998","journal-title":"Metab. Brain Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2913297","DOI":"10.1155\/2017\/2913297","article-title":"Pathogenic Roles of Glutamate Decarboxylase 65 Autoantibodies in Cerebellar Ataxias","volume":"2017","author":"Mitoma","year":"2017","journal-title":"J. Immunol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/ana.410100612","article-title":"Cerebellar degeneration in the rat following rapid correction of hyponatremia","volume":"10","author":"Norenberg","year":"1981","journal-title":"Ann. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1136\/jnnp.65.3.370","article-title":"Ataxia indued by small amounts of alcohol","volume":"65","author":"Setta","year":"1998","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/j.1530-0277.1987.tb01327.x","article-title":"Alcoholic cerebellar degeneration is not a dose-dependent phenomenon","volume":"11","author":"Estrin","year":"1987","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_49","first-page":"123","article-title":"Heterogeneity of human erythrocyte transketolase: A preliminary report","volume":"19","author":"Greenwood","year":"1984","journal-title":"Alcohol Alcohol."},{"key":"ref_50","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_51","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/j.1530-0277.2011.01662.x","article-title":"Relationship between liver function and brain shrinkage in patients with alcohol dependence","volume":"36","author":"Chen","year":"2012","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1007\/s12311-014-0636-6","article-title":"Ethanol-induced alterations in Purkinje neuron dendrites in adult and aging rats: A Review","volume":"14","author":"Dlugos","year":"2015","journal-title":"Cerebellum"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.2741\/e465","article-title":"Ethanol and adult CNS neurodamage: Oxidative stress, but possibly not excitotoxicity","volume":"4","author":"Collins","year":"2012","journal-title":"Front. Biosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s004390000346","article-title":"Genetic background of apparently idiopathic sporadic cerebellar ataxia","volume":"107","author":"Szymanski","year":"2000","journal-title":"Hum. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-013-1138-1","article-title":"Fragile X-associated tremor\/ataxia syndrome (FXTAS): Pathology and mechanisms","volume":"126","author":"Hagerman","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1111\/acer.14044","article-title":"Acute Ethanol Produces Ataxia and Induces Fmr1 Expression via Histone Modifications in the Rat Cerebellum","volume":"43","author":"Dulman","year":"2019","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2174\/157015908783769662","article-title":"Alcohol related changes in regulation of NMDA receptor functions","volume":"6","author":"Nagy","year":"2008","journal-title":"Curr. Neuropharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1002\/ana.410400207","article-title":"Positron emission tomographic studies of cerebral benzodiazepine-receptor binding in chronic alcoholics","volume":"40","author":"Gilman","year":"1996","journal-title":"Ann. Neurol."},{"key":"ref_59","first-page":"161","article-title":"Positron emission tomography-a tool for identifying the effects of alcohol dependence on the brain","volume":"27","author":"Wong","year":"2003","journal-title":"Alcohol Res. Health"},{"key":"ref_60","unstructured":"Johnson, R.T., Griffin, J.W., and McArthurm, J.V. (2002). Alcohol intoxication and withdrawal. Current Therapy in Neurologic Disease, Mosby. [7th ed.]."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s12311-014-0598-8","article-title":"Alcohol Withdrawal and Cerebellar Mitochondria","volume":"14","author":"Jung","year":"2014","journal-title":"Cerebellum"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s12311-020-01155-1","article-title":"Consensus paper: Cerebellum and social cognition","volume":"19","author":"Manto","year":"2020","journal-title":"Cerebellum"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1080\/14656566.2017.1349098","article-title":"Pharmacotherapy of alcoholism-an update on approved and off-label medications","volume":"18","author":"Soyka","year":"2017","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1001\/jama.2020.2012","article-title":"Treatment of alcohol use disorder","volume":"325","author":"Patel","year":"2021","journal-title":"JAMA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1007\/s12311-019-01041-5","article-title":"Consensus paper: Experimental neurostimulation of the cerebellum","volume":"18","author":"Miterko","year":"2019","journal-title":"Cerebellum"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s12311-010-0219-0","article-title":"Mechanisms of ethanol-induced death of cerebellar granule cell","volume":"11","author":"Luo","year":"2012","journal-title":"Cerebellum"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1177\/15353702-0323006-03","article-title":"Fetal alcohol spectrum disorders; an overview with emphasis on changes in brain and behavior","volume":"230","author":"Riley","year":"2005","journal-title":"Exp. Biol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1111\/acer.14040","article-title":"Fetal alcohol spectrum disorders: A review of the neurobehavioral deficits associated with prenatal alcohol exposure","volume":"43","author":"Mattson","year":"2019","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1111\/j.1530-0277.1990.tb01224.x","article-title":"Moderate prenatal alcohol exposure: Effects on child IQ and learning problems at age 7\u00bd years","volume":"14","author":"Streissguth","year":"1990","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/j.1530-0277.2002.tb02533.x","article-title":"Auditory and visual sustained attention in adolescents prenatally exposed to alcohol","volume":"26","author":"Coles","year":"2002","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_71","first-page":"557","article-title":"Patterns of cognitive-motor development in children with fetal alcohol syndrome from a community in South Africa","volume":"25","author":"Adnams","year":"2001","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.neuropsychologia.2005.07.016","article-title":"Effects of prenatal alcohol exposure on fine motor coordination and balance: A study of two adult samples","volume":"44","author":"Connor","year":"2006","journal-title":"Neuropsychologia"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1093\/brain\/awh729","article-title":"Cognition, emotion and the cerebellum","volume":"129","author":"Schmahmann","year":"2006","journal-title":"Brain"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1093\/brain\/awx317","article-title":"The cerebellar cognitive affective\/Schmahmann syndrome scale","volume":"141","author":"Hoche","year":"2018","journal-title":"Brain"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4729","DOI":"10.1093\/cercor\/bhaa020","article-title":"Graded cerebellar lobular volume deficits in adolescents and young adults with fetal alcohol spectrum disorders (FASD)","volume":"30","author":"Sullivan","year":"2020","journal-title":"Cereb. Cortex"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/cne.903620210","article-title":"Permanent neuronal cell loss in the cerebellum of rats exposed to continuous low blood alcohol levels during the brain growth spurt: A stereological investigation","volume":"362","author":"Napper","year":"1995","journal-title":"J. Comp. Neurol."},{"key":"ref_77","first-page":"726","article-title":"Fetal alcohol exposure and temporal vulnerability: Regional differences in cell loss as a function of the timing of binge-like alcohol exposure during brain development","volume":"23","author":"Maier","year":"1999","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0741-8329(00)00133-6","article-title":"Regional differences in cell loss associated with binge-like alcohol exposure during the first two trimesters equivalent in the rat","volume":"23","author":"Maier","year":"2001","journal-title":"Alcohol"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1080\/14734220410017338","article-title":"The effects of ethanol on the developing cerebellum and eyeblink classical conditioning","volume":"3","author":"Green","year":"2004","journal-title":"Cerebellum"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1111\/j.1530-0277.2008.00720.x","article-title":"Maturation-dependent alcohol resistance in the developing mouse: Cerebellar neuronal loss and gene expression during alcohol-vulnerable and -resistant periods","volume":"32","author":"Karacay","year":"2008","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_81","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_82","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/S0169-328X(01)00182-6","article-title":"Early postnatal ethanol exposure selectively decreases BDNF and truncated TrkB-T2 receptor mRNA expression in the rat cerebellum","volume":"93","author":"Light","year":"2001","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1007\/s00018-002-8475-x","article-title":"Chronic gestational exposure to ethanol impairs insulin-stimulated survival and mitochondrial function in cerebellar neurons","volume":"59","author":"Wands","year":"2002","journal-title":"Cell Mol. Life Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1046\/j.1471-4159.2000.0751035.x","article-title":"Chronic ethanol exposure attenuates the antiapoptotic effect of NMDA in cerebellar granule neurons","volume":"75","author":"Bhave","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0074-7742(03)56002-0","article-title":"NMDA receptors in alcoholism","volume":"56","author":"Hoffman","year":"2003","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1177\/1073858417712667","article-title":"Ethanol and the developing brain: Inhibition of neural activity and neuroapoptosis","volume":"24","author":"Lotfullina","year":"2018","journal-title":"Neuroscientist"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1080\/13556210410001717006","article-title":"Fetal alcohol syndrome at the cellular level","volume":"9","author":"Olney","year":"2004","journal-title":"Addict. Biol."},{"key":"ref_88","first-page":"81","article-title":"Focus on apoptosis to decipher how alcohol and many other drugs disrupt brain development","volume":"4","author":"Olney","year":"2014","journal-title":"Front. Pediatr."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1046\/j.1460-9568.2003.02765.x","article-title":"Too much of a good thing: Retinoic acid as an endogenous regulator of neural differentiation and exogenous teratogen","volume":"18","author":"McCaffery","year":"2003","journal-title":"Eur. J. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1111\/j.1530-0277.2010.01166.x","article-title":"Ethanol impairs activation of retinoic acid receptors in cerebellar granule cells in a rodent model of fetal alcohol spectrum disorders","volume":"34","author":"Kumar","year":"2010","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_91","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_92","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_93","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_94","doi-asserted-by":"crossref","first-page":"e1066","DOI":"10.1038\/cddis.2014.46","article-title":"TLR4 mediates the impairment of ubiquitin-proteasome and autophagy-lysosome pathways induced by ethanol treatment in brain","volume":"5","author":"Pla","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Mitoma, H., and Manto, M. (2019). Multi-actions of microglia. Neuroimmune Diseases. Form Cell to Living Brain, Springer.","DOI":"10.1007\/978-3-030-19515-1"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/B978-0-12-801284-0.00003-8","article-title":"Fetal alcohol spectrum disorders and neuroimmune changes","volume":"118","author":"Drew","year":"2014","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1111\/j.1530-0277.2010.01271.x","article-title":"Role of microglia in ethanol\u2019s apoptotic action on hypothalamic neuronal cells in primary cultures","volume":"34","author":"Boyadjieva","year":"2010","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ejmg.2016.10.005","article-title":"Interventions in fetal alcohol spectrum: An international perspective","volume":"60","author":"Petrenko","year":"2017","journal-title":"Eur. J. Med. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.3945\/ajcn.116.142075","article-title":"Randomized, double-blind, placebo-controlled clinical trial of choline supplementation in school-aged children with fetal alcohol spectrum disorders","volume":"104","author":"Nguyen","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.3945\/ajcn.114.099168","article-title":"Choline supplementation in children with fetal alcohol spectrum disorders: A randomized, double-blind, placebo-controlled trial","volume":"102","author":"Wozniak","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Granato, A., and Dering, B. (2018). Alcohol and the developing brain: Why neurons die and how survives change. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19102992"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e22681","DOI":"10.1002\/jbt.22681","article-title":"Ethanol exacerbates manganese-induced oxidative\/nitrosative stress, pro-inflammatory cytokines, nuclear factor-kB activation, and apoptosis induction in rat cerebellar cortex","volume":"35","author":"Nkpaa","year":"2021","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1002\/jnr.24797","article-title":"Ethanol modulation of cerebellar neuroinflammation in a postnatal mouse model of fetal alcohol spectrum disorders","volume":"99","author":"Kane","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s12311-020-01132-8","article-title":"Diagnostic criteria for primary autoimmune cerebellar ataxia (PACA)-Guidelines from an International Task Force on Immune Mediated Cerebellar Ataxia","volume":"19","author":"Hadjivassiliou","year":"2020","journal-title":"Cerebellum"}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/16\/8678\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:46:07Z","timestamp":1760165167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/16\/8678"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,18]]},"references-count":104,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijerph18168678"],"URL":"https:\/\/doi.org\/10.3390\/ijerph18168678","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,18]]}}}