The Effect of Chronic Ethanol Exposure and Thiamine Deficiency on Myelin-related Genes in the Cortex and the Cerebellum.
The Effect of Chronic Ethanol Exposure and Thiamine Deficiency on Myelin-related Genes in the Cortex and the Cerebellum.
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DOI：
10.1111/acer.14484
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Savage LM
中科院分区：
文献类型：
--
作者：
Chatterton BJ;Nunes PT;Savage LM
长期饮酒与大脑结构和功能异常有关。此外，持续暴露于乙醇（EtOH），营养缺乏症往往发展。硫胺素缺乏是酒精相关脑损伤的关键因素，并被怀疑有助于白色物质病理学。编码髓鞘蛋白质的基因在几个大脑皮层区域的表达改变与乙醇暴露。然而，关于硫胺素缺乏对髓鞘功能障碍的影响的研究有限。使用大鼠模型评估中度慢性EtOH暴露（CET;饮用水中20% EtOH，持续1个月或6个月）、吡啶硫胺诱导的硫胺素缺乏症治疗（PTD）、两种条件联合（CET-PTD）或CET+硫胺素注射（CET+T）对额叶和顶叶皮质和小脑中髓鞘相关基因表达（Olig 1、Olig 2、MBP、MAG和MOG）的影响。CET-PTD治疗对皮层中髓鞘相关基因的抑制最大。具体来说，顶叶皮层是最容易受到PTD-CET诱导的髓鞘相关基因改变的皮层区域。此外，PTD治疗，有和没有CET，引起轻微波动的几个髓鞘相关基因在额叶皮层的表达。相比之下，CET单独和PTD单独抑制小脑中的几个髓鞘相关基因。无论在哪个区域，髓鞘相关基因的显著恢复与延长禁欲和/或硫胺素恢复。中度慢性乙醇单独对皮质中髓鞘相关基因的抑制有轻微影响;然而，当与硫胺素缺乏结合时，减少被放大。在小脑长期乙醇和硫胺素缺乏后，髓鞘相关基因受到抑制。然而，髓鞘相关基因的抑制主要发生在乙醇去除后24小时或硫胺素恢复后;在禁欲或硫胺素恢复后三周内，基因表达反弹。
Long-term alcohol consumption has been linked to structural and functional brain abnormalities. Furthermore, with persistent exposure to ethanol (EtOH), nutrient deficiencies often develop. Thiamine deficiency is a key contributor to alcohol-related brain damage and is suspected to contribute to white matter pathology. The expression of genes encoding myelin proteins in several cortical brain regions is altered with EtOH exposure. However, there is limited research regarding the impact of thiamine deficiency on myelin dysfunction. A rat model was used to assess the impact of moderate chronic EtOH exposure (CET; 20% EtOH in drinking water for one or six months), pyrithiamine-induced thiamine deficiency treatment (PTD), both conditions combined (CET-PTD), or CET with thiamine injections (CET+T) on myelin-related gene expression (Olig1, Olig2, MBP, MAG, and MOG) in the frontal and parietal cortices and the cerebellum. The CET-PTD treatments caused the greatest suppression in myelin-related genes in the cortex. Specifically, the parietal cortex was the region that was most susceptible cortical to PTD-CET-induced alterations in myelin-related genes. In addition, PTD treatment, with and without CET, caused minor fluctuations in the expression of several myelin-related genes in the frontal cortex. In contrast, CET alone and PTD alone suppressed several myelin-related genes in the cerebellum. Regardless of the region, there was significant recovery of myelin-related genes with extended abstinence and/or thiamine restoration. Moderate chronic EtOH alone had a minor effect on the suppression of myelin-related genes in the cortex; however, when combined with thiamine deficiency, the reduction was amplified. There was a suppression of myelin-related genes following long-term EtOH and thiamine deficiency in the cerebellum. However, the suppression in the myelin-related genes mostly occurred 24-h after EtOH removal or following thiamine restoration; within three weeks of abstinence or thiamine recovery, gene expression rebounded.
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