Ethanol Administration in Mice Leads to Sex-Specific Changes in the Acetylation of α-Tubulin in the Cerebellum
Background: Acetylation of α-tubulin is an important post-translational modification that helps maintain microtubules’ stability and dynamics, including axonal transport, cell signaling, and overall neuronal integrity. This study investigates sex-based differences in alcohol-induced acetylation of α...
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MDPI AG
2025-03-01
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| author | Abosede Elesinnla Rehana Khatoon Nicholas Kleinert Junfang Wu Jaylyn Waddell Tibor Kristian |
| author_facet | Abosede Elesinnla Rehana Khatoon Nicholas Kleinert Junfang Wu Jaylyn Waddell Tibor Kristian |
| author_sort | Abosede Elesinnla |
| collection | DOAJ |
| description | Background: Acetylation of α-tubulin is an important post-translational modification that helps maintain microtubules’ stability and dynamics, including axonal transport, cell signaling, and overall neuronal integrity. This study investigates sex-based differences in alcohol-induced acetylation of α-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 α-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, α-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 (αTAT1), and the rate of ethanol metabolism-related acetyl-CoA production between male and female animals. |
| format | Article |
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| institution | DOAJ |
| issn | 2076-3425 |
| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-482c7f0a4087434c8c6ea6323e707d2f2025-08-20T03:14:27ZengMDPI AGBrain Sciences2076-34252025-03-0115432610.3390/brainsci15040326Ethanol Administration in Mice Leads to Sex-Specific Changes in the Acetylation of α-Tubulin in the CerebellumAbosede Elesinnla0Rehana Khatoon1Nicholas Kleinert2Junfang Wu3Jaylyn Waddell4Tibor Kristian5Department 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, USADepartment 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, USAVeterans Affairs Maryland Health Center System, 10 North Greene Street, Baltimore, MD 21201, USADepartment 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, USADepartment of Pediatrics, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201, USADepartment 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, USABackground: Acetylation of α-tubulin is an important post-translational modification that helps maintain microtubules’ stability and dynamics, including axonal transport, cell signaling, and overall neuronal integrity. This study investigates sex-based differences in alcohol-induced acetylation of α-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 α-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, α-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 (αTAT1), and the rate of ethanol metabolism-related acetyl-CoA production between male and female animals.https://www.mdpi.com/2076-3425/15/4/326ethanolcerebellumacetylationacetyl-CoAα-tubulin |
| spellingShingle | Abosede Elesinnla Rehana Khatoon Nicholas Kleinert Junfang Wu Jaylyn Waddell Tibor Kristian Ethanol Administration in Mice Leads to Sex-Specific Changes in the Acetylation of α-Tubulin in the Cerebellum Brain Sciences ethanol cerebellum acetylation acetyl-CoA α-tubulin |
| title | Ethanol Administration in Mice Leads to Sex-Specific Changes in the Acetylation of α-Tubulin in the Cerebellum |
| title_full | Ethanol Administration in Mice Leads to Sex-Specific Changes in the Acetylation of α-Tubulin in the Cerebellum |
| title_fullStr | Ethanol Administration in Mice Leads to Sex-Specific Changes in the Acetylation of α-Tubulin in the Cerebellum |
| title_full_unstemmed | Ethanol Administration in Mice Leads to Sex-Specific Changes in the Acetylation of α-Tubulin in the Cerebellum |
| title_short | Ethanol Administration in Mice Leads to Sex-Specific Changes in the Acetylation of α-Tubulin in the Cerebellum |
| title_sort | ethanol administration in mice leads to sex specific changes in the acetylation of α tubulin in the cerebellum |
| topic | ethanol cerebellum acetylation acetyl-CoA α-tubulin |
| url | https://www.mdpi.com/2076-3425/15/4/326 |
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