{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:30Z","timestamp":1787027730696,"version":"build-2736575974"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"Veterans Affairs","doi-asserted-by":"publisher","award":["BX004895"],"award-info":[{"award-number":["BX004895"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Veterans Affairs","doi-asserted-by":"publisher","award":["R01NS119275"],"award-info":[{"award-number":["R01NS119275"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Veterans Affairs","doi-asserted-by":"publisher","award":["R01AG077541"],"award-info":[{"award-number":["R01AG077541"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Veterans Affairs","doi-asserted-by":"publisher","award":["R01NS122777"],"award-info":[{"award-number":["R01NS122777"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH NINDS","award":["BX004895"],"award-info":[{"award-number":["BX004895"]}]},{"name":"NIH NINDS","award":["R01NS119275"],"award-info":[{"award-number":["R01NS119275"]}]},{"name":"NIH NINDS","award":["R01AG077541"],"award-info":[{"award-number":["R01AG077541"]}]},{"name":"NIH NINDS","award":["R01NS122777"],"award-info":[{"award-number":["R01NS122777"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Acetylation of \u03b1-tubulin is an important post-translational modification that helps maintain microtubules\u2019 stability and dynamics, including axonal transport, cell signaling, and overall neuronal integrity. This study investigates sex-based differences in alcohol-induced acetylation of \u03b1-tubulin in mouse cerebellum. Methods: Adult, 3-month-old male and female C57BL\/6 mice were administered 20% ethanol intraperitoneally. The cerebellum was dissected at 30 min, 1 h, 2 h, and 4 h post-injection. Expression levels of cerebellar acetylation of \u03b1-tubulin and enzymes mediating acetylation\/deacetylation were analyzed by Western blot. The downstream product of ethanol metabolism, acetyl-CoA, was quantified by HPLC. Results: In males, \u03b1-tubulin acetylation levels increased significantly as early as 30 min post-ethanol injection, whereas females exhibited increased acetylation at a later time point, after 1 h. These sex-specific changes coincided with alterations in acetyl-CoA levels that increased significantly at 15 min in males and 1 h in females following ethanol administration. Furthermore, the level of acetyltransferase that acetylates tubulin increased significantly at 30 min in males and 1 h in females. Notably, however, no significant changes were observed in the level of the tubulin deacetylating enzyme, HDAC6, in either sex. Conclusions: Our data demonstrate that these sex differences stem from variations in expression levels of tubulin acetyltransferase (\u03b1TAT1), and the rate of ethanol metabolism-related acetyl-CoA production between male and female animals.<\/jats:p>","DOI":"10.3390\/brainsci15040326","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T04:58:38Z","timestamp":1742533118000},"page":"326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ethanol Administration in Mice Leads to Sex-Specific Changes in the Acetylation of \u03b1-Tubulin in the Cerebellum"],"prefix":"10.3390","volume":"15","author":[{"given":"Abosede","family":"Elesinnla","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology (S.T.A.R.), University of Maryland School of Medicine, 685 Baltimore Street, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehana","family":"Khatoon","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology (S.T.A.R.), University of Maryland School of Medicine, 685 Baltimore Street, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Kleinert","sequence":"additional","affiliation":[{"name":"Veterans Affairs Maryland Health Center System, 10 North Greene Street, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3338-7291","authenticated-orcid":false,"given":"Junfang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology (S.T.A.R.), University of Maryland School of Medicine, 685 Baltimore Street, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaylyn","family":"Waddell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1804-8999","authenticated-orcid":false,"given":"Tibor","family":"Kristian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology (S.T.A.R.), University of Maryland School of Medicine, 685 Baltimore Street, Baltimore, MD 21201, USA"},{"name":"Veterans Affairs Maryland Health Center System, 10 North Greene Street, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.gene.2005.09.010","article-title":"Acetylation and deacetylation of non-histone proteins","volume":"363","author":"Glozak","year":"2005","journal-title":"Gene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119241","DOI":"10.1016\/j.bbamcr.2022.119241","article-title":"Direct and indirect effects of tubulin post-translational modifications on microtubule stability: Insights and regulations","volume":"1869","author":"Bar","year":"2022","journal-title":"Biochim. Biophys. Acta Mol. Cell. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10366","DOI":"10.1073\/pnas.1900441116","article-title":"Effects of alpha-tubulin acetylation on microtubule structure and stability","volume":"116","author":"Zhang","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","first-page":"821","article-title":"Chronic MAP4343 reverses escalated alcohol drinking in a mouse model of alcohol use disorder","volume":"48","author":"Macedo","year":"2023","journal-title":"Neuropsychopharmacology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1002\/hep.22481","article-title":"Alcohol-induced alterations in hepatic microtubule dynamics can be explained by impaired histone deacetylase 6 function","volume":"48","author":"Shepard","year":"2008","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.conb.2019.01.003","article-title":"Microtubule control of functional architecture in neurons","volume":"57","author":"Kelliher","year":"2019","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1177\/1535370219867296","article-title":"Microtubules: Evolving roles and critical cellular interactions","volume":"244","author":"Logan","year":"2019","journal-title":"Exp. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Waddell, J., Banerjee, A., and Kristian, T. (2021). Acetylation in Mitochondria Dynamics and Neurodegeneration. Cells, 10.","DOI":"10.3390\/cells10113031"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Labisso, W.L., Raulin, A.C., Nwidu, L.L., Kocon, A., Wayne, D., Erdozain, A.M., Morentin, B., Schwendener, D., Allen, G., and Enticott, J. (2018). The Loss of alpha- and beta-Tubulin Proteins Are a Pathological Hallmark of Chronic Alcohol Consumption and Natural Brain Ageing. Brain Sci., 8.","DOI":"10.3390\/brainsci8090175"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"jcs246702","DOI":"10.1242\/jcs.246702","article-title":"The role of the alpha-tubulin acetyltransferase alphaTAT1 in the DNA damage response","volume":"133","author":"Ryu","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Carmona, B., Marinho, H.S., Matos, C.L., Nolasco, S., and Soares, H. (2023). Tubulin Post-Translational Modifications: The Elusive Roles of Acetylation. Biology, 12.","DOI":"10.3390\/biology12040561"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Khatoon, R., Fick, J., Elesinnla, A., Waddell, J., and Kristian, T. (2024). Sexual Dimorphism of Ethanol-Induced Mitochondrial Dynamics in Purkinje Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252413714"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/s42255-021-00357-z","article-title":"Brain ethanol metabolism by astrocytic ALDH2 drives the behavioural effects of ethanol intoxication","volume":"3","author":"Jin","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S0022-3565(24)29435-0","article-title":"Acute ethanol administration oxidatively damages and depletes mitochondrial dna in mouse liver, brain, heart, and skeletal muscles: Protective effects of antioxidants","volume":"298","author":"Mansouri","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S0091-3057(01)00762-6","article-title":"The effect of cyanamide and 4-methylpyrazole on the ethanol-induced locomotor activity in mice","volume":"72","author":"Escarabajal","year":"2002","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1248\/bpb.b23-00140","article-title":"Astrocytic Responses to Binge Alcohol Intake in the Mouse Hindbrain","volume":"46","author":"Hasegawa","year":"2023","journal-title":"Biol. Pharm. Bull."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.neulet.2004.11.067","article-title":"Ethanol withdrawal reduces cerebellar parvalbumin expression in a manner reversed by estrogens","volume":"377","author":"Rewal","year":"2005","journal-title":"Neurosci. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/1471-2164-7-308","article-title":"Ethanol sensitivity: A central role for CREB transcription regulation in the cerebellum","volume":"7","author":"Misra","year":"2006","journal-title":"BMC Genom."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s11064-006-9127-6","article-title":"Microtubule deacetylases, SirT2 and HDAC6, in the nervous system","volume":"32","author":"Southwood","year":"2007","journal-title":"Neurochem. Res."},{"key":"ref_20","first-page":"1","article-title":"Brain ethanol metabolism and mitochondria","volume":"23","author":"Waddell","year":"2022","journal-title":"Curr. Top. Biochem. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"109638","DOI":"10.1016\/j.mehy.2020.109638","article-title":"Ethanol metabolism: The good, the bad, and the ugly","volume":"140","author":"Wilson","year":"2020","journal-title":"Med. Hypotheses"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.tins.2021.09.006","article-title":"Alcohol and the brain: From genes to circuits","volume":"44","author":"Egervari","year":"2021","journal-title":"Trends Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5878","DOI":"10.1038\/s41467-021-25786-y","article-title":"ATP-citrate lyase promotes axonal transport across species","volume":"12","author":"Even","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Erdozain, A.M., Morentin, B., Bedford, L., King, E., Tooth, D., Brewer, C., Wayne, D., Johnson, L., Gerdes, H.K., and Wigmore, P. (2014). Alcohol-related brain damage in humans. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093586"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"G373","DOI":"10.1152\/ajpgi.00026.2019","article-title":"Alcohol-induced microtubule acetylation leads to the accumulation of large, immobile lipid droplets","volume":"317","author":"Groebner","year":"2019","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.jhep.2005.07.007","article-title":"Microtubules are more stable and more highly acetylated in ethanol-treated hepatic cells","volume":"44","author":"Kannarkat","year":"2006","journal-title":"J. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e34805","DOI":"10.1371\/journal.pone.0034805","article-title":"SIRT2 ablation has no effect on tubulin acetylation in brain, cholesterol biosynthesis or the progression of Huntington's disease phenotypes in vivo","volume":"7","author":"Bobrowska","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1038\/ncomms2962","article-title":"alphaTAT1 is the major alpha-tubulin acetyltransferase in mice","volume":"4","author":"Kalebic","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21517","DOI":"10.1073\/pnas.1013728107","article-title":"The major alpha-tubulin K40 acetyltransferase alphaTAT1 promotes rapid ciliogenesis and efficient mechanosensation","volume":"107","author":"Shida","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1016\/j.neuropharm.2012.01.011","article-title":"Changes in histone acetylation in the prefrontal cortex of ethanol-exposed adolescent rats are associated with ethanol-induced place conditioning","volume":"62","author":"Pascual","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1007\/s11033-019-04733-7","article-title":"Correlation between the epigenetic modification of histone H3K9 acetylation of NR2B gene promoter in rat hippocampus and ethanol withdrawal syndrome","volume":"46","author":"Li","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/s41586-019-1700-7","article-title":"Alcohol metabolism contributes to brain histone acetylation","volume":"574","author":"Mews","year":"2019","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1002\/syn.20947","article-title":"Enhancement of histone acetylation in midbrain of mice with ethanol physical dependence and its withdrawal","volume":"65","author":"Shibasaki","year":"2011","journal-title":"Synapse"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/15\/4\/326\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:57:39Z","timestamp":1760029059000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/15\/4\/326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,21]]},"references-count":34,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["brainsci15040326"],"URL":"https:\/\/doi.org\/10.3390\/brainsci15040326","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,21]]}}}