{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:35:33Z","timestamp":1788305733666,"version":"build-2803163510"},"reference-count":88,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS055215\/R0NS108779"],"award-info":[{"award-number":["R01NS055215\/R0NS108779"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Ischemic stroke triggers a series of complex pathophysiological processes including autophagy. Differential activation of autophagy occurs in neurons derived from males versus females after stressors such as nutrient deprivation. Whether autophagy displays sexual dimorphism after ischemic stroke is unknown. We used a cerebral ischemia mouse model (middle cerebral artery occlusion, MCAO) to evaluate the effects of inhibiting autophagy in ischemic brain pathology. We observed that inhibiting autophagy reduced infarct volume in males and ovariectomized females. However, autophagy inhibition enhanced infarct size in females and in ovariectomized females supplemented with estrogen compared to control mice. We also observed that males had increased levels of Beclin1 and LC3 and decreased levels of pULK1 and p62 at 24 h, while females had decreased levels of Beclin1 and increased levels of ATG7. Furthermore, the levels of autophagy markers were increased under basal conditions and after oxygen and glucose deprivation in male neurons compared with female neurons in vitro. E2 supplementation significantly inhibited autophagy only in male neurons, and was beneficial for cell survival only in female neurons. This study shows that autophagy in the ischemic brain differs between the sexes, and that autophagy regulators have different effects in a sex-dependent manner in neurons.<\/jats:p>","DOI":"10.3390\/cells10071825","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T11:26:10Z","timestamp":1626780370000},"page":"1825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Sex-Specific Differences in Autophagic Responses to Experimental Ischemic Stroke"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7153-9028","authenticated-orcid":false,"given":"Anthony N.","family":"Patrizz","sequence":"first","affiliation":[{"name":"Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2139-6134","authenticated-orcid":false,"given":"Jose F.","family":"Moruno-Manchon","sequence":"additional","affiliation":[{"name":"Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena M.","family":"O\u2019Keefe","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beth Israel Deaconess Hospital, 330 Brookline Avenue, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Doran","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venugopal R.","family":"Venna","sequence":"additional","affiliation":[{"name":"Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey S.","family":"Tsvetkov","sequence":"additional","affiliation":[{"name":"Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise D.","family":"McCullough","sequence":"additional","affiliation":[{"name":"Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1161\/01.STR.0000199613.38911.b2","article-title":"The lifetime risk of stroke: Estimates from the Framingham Study","volume":"37","author":"Seshadri","year":"2006","journal-title":"Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1161\/STROKEAHA.108.542894","article-title":"Gender differences in stroke incidence and poststroke disability in the Framingham heart study","volume":"40","author":"Petrea","year":"2009","journal-title":"Stroke"},{"key":"ref_3","first-page":"e2","article-title":"American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart disease and stroke statistics\u20142012 update: A report from the American Heart Association","volume":"125","author":"Roger","year":"2012","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1159\/000102141","article-title":"Evidence for age-dependent education-related differences in men and women with first-ever stroke. Results from a community-based incidence study in northern Sweden","volume":"28","author":"Lofmark","year":"2007","journal-title":"Neuroepidemiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1111\/j.1471-4159.2006.04269.x","article-title":"Specific caspase inhibitor Q-VD-OPh prevents neonatal stroke in P7 rat: A role for gender","volume":"100","author":"Renolleau","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11662","DOI":"10.1073\/pnas.1102635108","article-title":"miR-23a regulation of X-linked inhibitor of apoptosis (XIAP) contributes to sex differences in the response to cerebral ischemia","volume":"108","author":"Siegel","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1111\/j.1471-4159.2004.02547.x","article-title":"PARP-1 gene disruption in mice preferentially protects males from perinatal brain injury","volume":"90","author":"Hagberg","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1161\/STROKEAHA.110.594861","article-title":"Sex differences in the response to poly(ADP-ribose) polymerase-1 deletion and caspase inhibition after stroke","volume":"42","author":"Liu","year":"2011","journal-title":"Stroke"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1212\/01.wnl.0000237024.16438.20","article-title":"Projected costs of ischemic stroke in the United States","volume":"67","author":"Brown","year":"2006","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1161\/STR.0b013e31829734f2","article-title":"American Heart Association Advocacy Coordinating Committee and Stroke Council Forecasting the future of stroke in the United States: A policy statement from the American Heart Association and American Stroke Association","volume":"44","author":"Ovbiagele","year":"2013","journal-title":"Stroke"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1212\/WNL.0b013e3182762397","article-title":"The global burden of stroke and need for a continuum of care","volume":"80","author":"Norrving","year":"2013","journal-title":"Neurology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1038\/nrm2529","article-title":"Autophagic cell death: The story of a misnomer","volume":"9","author":"Kroemer","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.molcel.2010.09.023","article-title":"Autophagy and the integrated stress response","volume":"40","author":"Kroemer","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/ncb0910-814","article-title":"Eaten alive: A history of macroautophagy","volume":"12","author":"Yang","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nature09782","article-title":"Autophagy in immunity and inflammation","volume":"469","author":"Levine","year":"2011","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nature06639","article-title":"Autophagy fights disease through cellular self-digestion","volume":"451","author":"Mizushima","year":"2008","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.biocel.2011.01.006","article-title":"Autophagosomes and human diseases","volume":"43","author":"Beau","year":"2011","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1111\/j.1582-4934.2011.01293.x","article-title":"On the role of autophagy in human diseases: A gender perspective","volume":"15","author":"Lista","year":"2011","journal-title":"J. Cell Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"762","DOI":"10.4161\/auto.6412","article-title":"Neuronal injury in rat model of permanent focal cerebral ischemia is associated with activation of autophagic and lysosomal pathways","volume":"4","author":"Wen","year":"2008","journal-title":"Autophagy"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/ana.21714","article-title":"Postischemic treatment of neonatal cerebral ischemia should target autophagy","volume":"66","author":"Puyal","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"482","DOI":"10.4161\/auto.6.4.11737","article-title":"Autophagy activation is associated with neuroprotection in a rat model of focal cerebral ischemic preconditioning","volume":"6","author":"Sheng","year":"2010","journal-title":"Autophagy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.brainres.2011.05.049","article-title":"Autophagy activation is involved in neuroprotection induced by hyperbaric oxygen preconditioning against focal cerebral ischemia in rats","volume":"1402","author":"Yan","year":"2011","journal-title":"Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/s12031-011-9575-6","article-title":"Role of autophagy in early brain injury after experimental subarachnoid hemorrhage","volume":"46","author":"Wang","year":"2012","journal-title":"J. Mol. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s10059-010-0130-z","article-title":"Propofol protects the autophagic cell death induced by the ischemia\/reperfusion injury in rats","volume":"30","author":"Noh","year":"2010","journal-title":"Mol. Cells"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/NEN.0b013e31821352bd","article-title":"Severe global cerebral ischemia-induced programmed necrosis of hippocampal CA1 neurons in rat is prevented by 3-methyladenine: A widely used inhibitor of autophagy","volume":"70","author":"Wang","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Jiang, Y., Zhu, J., Wu, L., Xu, G., Dai, J., and Liu, X. (2012). Tetracycline inhibits local inflammation induced by cerebral ischemia via modulating autophagy. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048672"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.neuroscience.2013.04.054","article-title":"Propofol prevents cerebral ischemia-triggered autophagy activation and cell death in the rat hippocampus through the NF-kappaB\/p53 signaling pathway","volume":"246","author":"Cui","year":"2013","journal-title":"Neuroscience"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.neuroscience.2013.10.046","article-title":"Autophagy in the brain of neonates following hypoxia-ischemia shows sex- and region-specific effects","volume":"256","author":"Weis","year":"2014","journal-title":"Neuroscience"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/ana.10356","article-title":"Intravenous TAT-Bcl-Xl is protective after middle cerebral artery occlusion in mice","volume":"52","author":"Kilic","year":"2002","journal-title":"Ann. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.expneurol.2012.05.019","article-title":"Protection from cerebral ischemia by inhibition of TGFbeta-activated kinase","volume":"237","author":"White","year":"2012","journal-title":"Exp. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.expneurol.2004.01.004","article-title":"Chronic behavioral testing after focal ischemia in the mouse: Functional recovery and the effects of gender","volume":"187","author":"Li","year":"2004","journal-title":"Exp. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jns.2007.12.034","article-title":"Akt1 gene deletion and stroke","volume":"269","author":"Li","year":"2008","journal-title":"J. Neurol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1093\/jn\/105.8.1003","article-title":"Effect upon brain weight and cholesterol content of maintaining rats of various ages at constant weight","volume":"105","author":"Chevallier","year":"1975","journal-title":"J. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16364","DOI":"10.1073\/pnas.0605342103","article-title":"Stability of inbred mouse strain differences in behavior and brain size between laboratories and across decades","volume":"103","author":"Wahlsten","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8701","DOI":"10.1523\/JNEUROSCI.23-25-08701.2003","article-title":"Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection","volume":"23","author":"McCullough","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1365-2826.2011.02248.x","article-title":"Effects of chronic and acute oestrogen replacement therapy in aged animals after experimental stroke","volume":"24","author":"Liu","year":"2012","journal-title":"J. Neuroendocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"20493","DOI":"10.1074\/jbc.M409985200","article-title":"Pharmacological inhibition of AMP-activated protein kinase provides neuroprotection in stroke","volume":"280","author":"McCullough","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"15213","DOI":"10.1038\/srep15213","article-title":"Cytoplasmic sphingosine-1-phosphate pathway modulates neuronal autophagy","volume":"5","author":"Uzor","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1093\/hmg\/ddx046","article-title":"Inhibiting sphingosine kinase 2 mitigates mutant Huntingtin-induced neurodegeneration in neuron models of Huntington disease","volume":"26","author":"Uzor","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.18632\/aging.101282","article-title":"The G-quadruplex DNA stabilizing drug pyridostatin promotes DNA damage and downregulates transcription of Brca1 in neurons","volume":"9","author":"Koellhoffer","year":"2017","journal-title":"Aging"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1080\/09168451.2016.1194180","article-title":"A qPCR method to characterize the sex type of the cell strains from rats","volume":"80","author":"Xiang","year":"2016","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.18632\/aging.101144","article-title":"TFEB ameliorates the impairment of the autophagy-lysosome pathway in neurons induced by doxorubicin","volume":"8","author":"Uzor","year":"2016","journal-title":"Aging"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.mcn.2017.11.014","article-title":"Peroxisomes contribute to oxidative stress in neurons during doxorubicin-based chemotherapy","volume":"86","author":"Uzor","year":"2018","journal-title":"Mol. Cell Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Moruno-Manchon, J.F., Uzor, N.E., Ambati, C.R., Shetty, V., Putluri, N., Jagannath, C., McCullough, L.D., and Tsvetkov, A.S. (2018). Sphingosine kinase 1-associated autophagy differs between neurons and astrocytes. Cell Death Dis., 9.","DOI":"10.1038\/s41419-018-0599-5"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1038\/jcbfm.2009.5","article-title":"Changes in experimental stroke outcome across the life span","volume":"29","author":"Liu","year":"2009","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/jcbfm.2014.186","article-title":"Sex differences in ischemic stroke sensitivity are influenced by gonadal hormones, not by sex chromosome complement","volume":"35","author":"Manwani","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1002\/cne.21974","article-title":"Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain","volume":"513","author":"Azevedo","year":"2009","journal-title":"J. Comp. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.conb.2018.02.008","article-title":"Neuronal autophagy and intercellular regulation of homeostasis in the brain","volume":"51","author":"Kulkarni","year":"2018","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sanchez-Martin, P., and Komatsu, M. (2018). p62\/SQSTM1\u2014Steering the cell through health and disease. J. Cell Sci., 131.","DOI":"10.1242\/jcs.222836"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bresciani, A., Spiezia, M.C., Boggio, R., Cariulo, C., Nordheim, A., Altobelli, R., Kuhlbrodt, K., Dominguez, C., Munoz-Sanjuan, I., and Wityak, J. (2018). Quantifying autophagy using novel LC3B and p62 TR-FRET assays. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194423"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Yoshii, S.R., and Mizushima, N. (2017). Monitoring and Measuring Autophagy. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091865"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)","volume":"12","author":"Klionsky","year":"2016","journal-title":"Autophagy"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"33889","DOI":"10.1074\/jbc.273.51.33889","article-title":"A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy","volume":"273","author":"Mizushima","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/26506","article-title":"A protein conjugation system essential for autophagy","volume":"395","author":"Mizushima","year":"1998","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Moruno-Manchon, J.F., Lejault, P., Wang, Y., McCauley, B., Honarpisheh, P., Morales Scheihing, D.A., Singh, S., Dang, W., Kim, N., and Urayama, A. (2020). Small-molecule G-quadruplex stabilizers reveal a novel pathway of autophagy regulation in neurons. eLife, 9.","DOI":"10.7554\/eLife.52283"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1038\/cddis.2010.9","article-title":"The novel estrogen-induced gene EIG121 regulates autophagy and promotes cell survival under stress","volume":"1","author":"Deng","year":"2010","journal-title":"Cell Death Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e1812","DOI":"10.1038\/cddis.2015.181","article-title":"Estrogen receptor alpha regulates non-canonical autophagy that provides stress resistance to neuroblastoma and breast cancer cells and involves BAG3 function","volume":"6","author":"Felzen","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ceb.2009.11.015","article-title":"Hypoxia-induced autophagy: Cell death or cell survival?","volume":"22","author":"Mazure","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1161\/01.STR.0000196957.55928.ab","article-title":"Time is brain\u2014Quantified","volume":"37","author":"Saver","year":"2006","journal-title":"Stroke"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"422","DOI":"10.4161\/auto.5778","article-title":"Apoptosis meets autophagy-like cell death in the ischemic penumbra: Two sides of the same coin?","volume":"4","author":"Rami","year":"2008","journal-title":"Autophagy"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.semcancer.2013.05.007","article-title":"Autophagosome formation--the role of ULK1 and Beclin1-PI3KC3 complexes in setting the stage","volume":"23","author":"Wirth","year":"2013","journal-title":"Semin. Cancer Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e23873","DOI":"10.1097\/MD.0000000000023873","article-title":"Effects of autophagy inhibitor 3-Methyladenine on ischemic stroke: A protocol for systematic review and meta-analysis","volume":"100","author":"Zhang","year":"2021","journal-title":"Medicine"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Wang, M., Liang, X., Cheng, M., Yang, L., Liu, H., Wang, X., Sai, N., and Zhang, X. (2019). Homocysteine enhances neural stem cell autophagy in in vivo and in vitro model of ischemic stroke. Cell Death Dis., 10.","DOI":"10.1038\/s41419-019-1798-4"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1111\/j.1755-5949.2012.00295.x","article-title":"Excessive autophagy contributes to neuron death in cerebral ischemia","volume":"18","author":"Shi","year":"2012","journal-title":"CNS Neurosci. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1007\/s11064-018-2599-3","article-title":"Ischemic Postconditioning Alleviates Cerebral Ischemia-Reperfusion Injury Through Activating Autophagy During Early Reperfusion in Rats","volume":"43","author":"Sun","year":"2018","journal-title":"Neurochem. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4788","DOI":"10.1073\/pnas.1100844108","article-title":"Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK","volume":"108","author":"Shang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1111\/ejn.14731","article-title":"Insight into the molecular sex dimorphism of ischaemic stroke in rat cerebral cortex: Focus on neuroglobin, sex steroids and autophagy","volume":"52","author":"Burguete","year":"2020","journal-title":"Eur. J. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.4161\/auto.7.10.16608","article-title":"Beclin 1-independent autophagy contributes to apoptosis in cortical neurons","volume":"7","author":"Grishchuk","year":"2011","journal-title":"Autophagy"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/ncb2757","article-title":"ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase","volume":"15","author":"Russell","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s12264-016-0017-x","article-title":"Inhibition of Autophagy by Estradiol Promotes Locomotor Recovery after Spinal Cord Injury in Rats","volume":"32","author":"Lin","year":"2016","journal-title":"Neurosci. Bull."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1074\/jbc.M804396200","article-title":"Starving neurons show sex difference in autophagy","volume":"284","author":"Du","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"457","DOI":"10.4161\/auto.7.5.14226","article-title":"Autophagic cell death: Loch Ness monster or endangered species?","volume":"7","author":"Shen","year":"2011","journal-title":"Autophagy"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1161\/STROKEAHA.108.538686","article-title":"Sex differences in caspase activation after stroke","volume":"40","author":"Liu","year":"2009","journal-title":"Stroke"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"273","DOI":"10.4161\/auto.5.2.7640","article-title":"To die or to live: The dual role of poly(ADP-ribose) polymerase-1 in autophagy and necrosis under oxidative stress and DNA damage","volume":"5","author":"Huang","year":"2009","journal-title":"Autophagy"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1080\/15548627.2019.1703354","article-title":"Differential regulation of autophagy during metabolic stress in astrocytes and neurons","volume":"16","author":"Kulkarni","year":"2019","journal-title":"Autophagy"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1080\/15548627.2016.1183082","article-title":"SPHK1\/sphingosine kinase 1-mediated autophagy differs between neurons and SH-SY5Y neuroblastoma cells","volume":"12","author":"Uzor","year":"2016","journal-title":"Autophagy"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Sharma, J., Nelluru, G., Wilson, M.A., Johnston, M.V., and Hossain, M.A. (2011). Sex-specific activation of cell death signalling pathways in cerebellar granule neurons exposed to oxygen glucose deprivation followed by reoxygenation. ASN Neuro, 3.","DOI":"10.1042\/AN20100032"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.neuroscience.2012.05.048","article-title":"Mechanism of the sex difference in neuronal ischemic cell death","volume":"219","author":"Fairbanks","year":"2012","journal-title":"Neuroscience"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.neuroscience.2011.09.053","article-title":"Isoflurane preconditioning protects neurons from male and female mice against oxygen and glucose deprivation and is modulated by estradiol only in neurons from female mice","volume":"199","author":"Johnsen","year":"2011","journal-title":"Neuroscience"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1749-6632.2012.06668.x","article-title":"The ischemic penumbra: How does tissue injury evolve?","volume":"1268","author":"Heiss","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.cell.2011.07.030","article-title":"Autophagy and aging","volume":"146","author":"Rubinsztein","year":"2011","journal-title":"Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S0531-5565(03)00002-0","article-title":"Ageing-related changes in the in vivo function of rat liver macroautophagy and proteolysis","volume":"38","author":"Vittorini","year":"2003","journal-title":"Exp. Gerontol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1080\/15548627.2020.1840796","article-title":"Ischemia-induced upregulation of autophagy preludes dysfunctional lysosomal storage and associated synaptic impairments in neurons","volume":"17","author":"Zhang","year":"2021","journal-title":"Autophagy"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1080\/15548627.2020.1752511","article-title":"Sex differences in autophagy-mediated diseases: Toward precision medicine","volume":"17","author":"Shang","year":"2021","journal-title":"Autophagy"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nrg3687","article-title":"X chromosome regulation: Diverse patterns in development, tissues and disease","volume":"15","author":"Deng","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1056\/NEJM199307223290429","article-title":"Women in clinical trials of new drugs. A change in Food and Drug Administration policy. The Working Group on Women in Clinical Trials","volume":"329","author":"Merkatz","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/509282a","article-title":"Policy: NIH to balance sex in cell and animal studies","volume":"509","author":"Clayton","year":"2014","journal-title":"Nature"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/7\/1825\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:32:14Z","timestamp":1760164334000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/7\/1825"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,20]]},"references-count":88,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["cells10071825"],"URL":"https:\/\/doi.org\/10.3390\/cells10071825","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,20]]}}}