Chronic Exposure to Alcohol Inhibits New Myelin Generation in Adult Mouse Brain

Chronic alcohol consumption causes cognitive impairments accompanying with white matter atrophy. Recent evidence has shown that myelin dynamics remain active and are important for brain functions in adulthood. For example, new myelin generation is required for learning and memory functions. However, it remains undetermined whether alcohol exposure can alter myelin dynamics in adulthood. In this study, we examine the effect of chronic alcohol exposure on myelin dynamics by using genetic approaches to label newly generated myelin (NG2-CreERt; mT/mG). Our results indicated that alcohol exposure (either 5% or 10% in drinking water) for 3 weeks remarkably reduced mGFP + /NG2- new myelin and mGFP + /CC1 + new oligodendrocytes in the prefrontal cortex and corpus callosum of 6-month-old NG2-CreERt; mT/mG mice as compared to controls without changing the mGFP + /NG2 + oligodendrocyte precursor cells (OPCs) density, suggesting that alcohol exposure may inhibit oligodendrocyte differentiation. In support with these findings, the alcohol exposure did not significantly alter apoptotic cell number or overall MBP expression in the brains. Further, the alcohol exposure decreased the histone deacetylase1 (HDAC1) expression in mGFP + /NG2 + OPCs, implying epigenetic mechanisms were involved in the arrested OPC differentiation. Together, our results indicate that chronic exposure to alcohol can inhibit myelinogenesis in the adult mouse brain and that may contribute to alcohol-related cognitive impairments.

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NMDA in adult mouse brain: Mechanism of learning deficits prevention after prenatal alcohol exposure

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2005.10.060 ◽

2005 ◽

Vol 193 (6) ◽

pp. S24

Author(s):

Laura Toso ◽

Robin Roberson ◽

Jade Woodard ◽

Daniel Abebe ◽

Sarah Poggi ◽

...

Keyword(s):

Mouse Brain ◽

Adult Mouse ◽

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

Adult Mouse Brain ◽

Learning Deficits ◽

Brain Mechanism ◽

Prenatal Alcohol

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Distribution of synuclein family mRNAs in adult mouse brain

Neuroscience Research ◽

10.1016/s0168-0102(00)81568-0 ◽

2000 ◽

Vol 38 ◽

pp. S120

Author(s):

A Ninomiya

Keyword(s):

Mouse Brain ◽

Adult Mouse ◽

Adult Mouse Brain

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Faculty Opinions recommendation of Genome-wide atlas of gene expression in the adult mouse brain.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1057954.521603 ◽

2007 ◽

Author(s):

Matteo Carandini

Keyword(s):

Gene Expression ◽

Mouse Brain ◽

Adult Mouse ◽

Adult Mouse Brain ◽

Genome Wide

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Correlated 5-Hydroxymethylcytosine (5hmC) and Gene Expression Profiles Underpin Gene and Organ-Specific Epigenetic Regulation in Adult Mouse Brain and Liver

PLoS ONE ◽

10.1371/journal.pone.0170779 ◽

2017 ◽

Vol 12 (1) ◽

pp. e0170779 ◽

Cited By ~ 30

Author(s):

I-Hsuan Lin ◽

Yi-Fan Chen ◽

Ming-Ta Hsu

Keyword(s):

Gene Expression ◽

Mouse Brain ◽

Epigenetic Regulation ◽

Adult Mouse ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Adult Mouse Brain ◽

Organ Specific

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Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00278.2014 ◽

2014 ◽

Vol 307 (9) ◽

pp. G941-G949 ◽

Cited By ~ 8

Author(s):

Padmanabhan Srinivasan ◽

Rubina Kapadia ◽

Arundhati Biswas ◽

Hamid M. Said

Keyword(s):

Transgenic Mice ◽

Chronic Exposure ◽

Methylation Status ◽

Acinar Cells ◽

Alcohol Exposure ◽

Significant Inhibition ◽

Pancreatic Acinar Cells ◽

Chronic Alcohol ◽

Wild Type ◽

Chronic Alcohol Exposure

Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5′-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na+ dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.

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