Chloride intracellular channel 4 (CLIC4) expression profile in the mouse medial prefrontal cortex and its regulation by ethanol.

Chloride intracellular channel 4 (CLIC4) expression profile in the mouse medial prefrontal cortex and its regulation by ethanol.
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小鼠内侧前额叶皮层中的氯化物内通道4(CLIC4)表达谱及其对乙醇的调节。

DOI:
10.1111/acer.14754
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发表时间:
2022-01
期刊:
Alcoholism, clinical and experimental research
影响因子:
--
通讯作者:
Miles MF
Miles MF
中科院分区:
其他
文献类型:
--
作者:
Bogenpohl JW;Weston RM;Foreman TN;Kitchen KE;Miles MF

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氯离子胞内通道4 (CLIC4)是一种多功能的变质蛋白,越来越多的证据支持它在大脑对乙醇的分子和行为反应中发挥重要作用。尽管了解这一作用背后的功能生物学是关键,但对大脑中CLIC4的细胞和亚细胞表达模式以及它们如何受到乙醇的影响知之甚少。采用qRT-PCR方法检测C57BL/6J小鼠在急性乙醇暴露和无乙醇暴露情况下内侧前额叶皮层(mPFC)中Clic4 mRNA的表达。采用两种互补的免疫组织化学技术来评估CLIC4蛋白的亚细胞定位,以及在急性乙醇缺乏和存在的情况下,它在mPFC中不同脑细胞类型的表达模式。通过免疫组织化学和体视学技术,我们发现CLIC4蛋白在少突胶质细胞(最丰富)、小胶质细胞和星形胶质细胞中大量表达,在神经元中表达最少。在急性乙醇作用下,我们观察到雌性小鼠而非雄性小鼠的Clic4 mRNA表达迅速增加,表达Clic4蛋白的少突胶质细胞和星形胶质细胞数量总体增加。这些发现表明,Clic4作为大脑急性乙醇的早期反应基因,可能是其调节乙醇行为能力的基础。此外,我们的研究结果表明,CLIC4在大脑对乙醇的反应中的作用可能是通过少突胶质细胞介导的。
Chloride intracellular channel 4 (CLIC4) is a multifunctional metamorphic protein with a growing body of evidence supporting a major role in the brain’s molecular and behavioral response to ethanol. Although key to understanding the functional biology underlying this role, little is known about the cellular and subcellular expression patterns of CLIC4 in brain and how they are affected by ethanol. qRT-PCR was used to assess Clic4 mRNA expression in medial prefrontal cortex (mPFC) of C57BL/6J mice in the absence and presence of acute ethanol exposure. Two complementary immunohistochemical techniques were employed to assess the subcellular localization of CLIC4 protein, as well as its pattern of expression across brain cell types in mPFC in the absence and presence of acute ethanol. Through immunohistochemical and stereological techniques, we show that CLIC4 protein is robustly expressed by oligodendrocytes (most abundant), microglia, and astrocytes, with minimal expression in neurons. Following acute ethanol, we observed a rapid increase in Clic4 mRNA expression in female but not male mice and an overall increase in the number of oligodendrocytes and astrocytes expressing CLIC4 protein. These findings suggest a function for Clic4 as an early response gene for acute ethanol in brain, which likely underlies its ability to modulate ethanol behavior. Furthermore, our results suggest the role of CLIC4 in the brain’s response to ethanol is likely mediated through oligodendrocytes.
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