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首页> 外文期刊>Alcohol >Localization of brain 5α-reductase messenger RNA in mice selectively bred for high chronic alcohol withdrawal severity
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Localization of brain 5α-reductase messenger RNA in mice selectively bred for high chronic alcohol withdrawal severity

机译：选择性饲养小鼠中大脑5α-还原酶信使RNA的定位，以提高慢性酒精戒断的严重程度

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Several lines of evidence suggest that fluctuations in endogenous levels of the γ-aminobutyric acid (GABA)ergic neurosteroid allopregnanolone (ALLO) represent one mechanism for regulation of GABAergic inhibitory tone in the brain, with an ultimate impact on behavior. Consistent with this idea, there was an inverse relationship between ALLO levels and symptoms of anxiety and depression in humans and convulsive activity in rodents during alcohol withdrawal. Our recent studies examined the activity and expression of 5α-reductase (Srd5a1), the rate-limiting enzyme in the biosynthesis of ALLO, during alcohol withdrawal in mice selectively bred for high chronic alcohol withdrawal (Withdrawal Seizure-Prone [WSP]) and found that Srd5a1 was downregulated in the cortex and hippocampus over the time course of dependence and withdrawal. The purpose of the present studies was to extend these findings and more discretely map the regions of Srd5a1 expression in mouse brain using radioactive in situ hybridization in WSP mice that were ethanol na?ve, following exposure to 72. h ethanol vapor (dependent) or during peak withdrawal. In na?ve animals, expression of Srd5a1 was widely distributed throughout the mouse brain, with highest expression in specific regions of the cerebral cortex, hippocampus, thalamus, hypothalamus, and amygdala. In dependent animals and during withdrawal, there was no change in Srd5a1 expression in cortex or hippocampus, which differed from our recent findings in dissected tissues. These results suggest that local Srd5a1 mRNA expression in WSP brain may not change in parallel with local ALLO content or withdrawal severity.
机译：几条证据表明，γ-氨基丁酸（GABA）能量神经甾体Allopregnanolone（ALLO）内源性水平的波动代表了大脑中GABA抑制音调的一种机制，最终对行为产生了影响。与此想法一致，在戒酒期间，ALLO水平与人类焦虑和抑郁症状与啮齿类动物的抽搐活动之间存在反比关系。我们最近的研究检查了选择性饲养高慢性酒精戒断小鼠（戒断癫痫发作[WSP]）的小鼠戒酒期间5α-还原酶（Srd5a1）（ALLO生物合成中的限速酶）的活性和表达，发现在依赖和戒断的过程中，Srd5a1在皮层和海马中被下调。本研究的目的是扩展这些发现，并在暴露于72 h乙醇蒸汽（依赖）或乙醇暴露的WSP小鼠中，使用纯净的WSP小鼠中的放射性原位杂交，更离散地绘制Srd5a1在小鼠脑中表达的区域。在撤退高峰期。在幼稚动物中，Srd5a1的表达广泛分布于整个小鼠大脑，在大脑皮层，海马，丘脑，下丘脑和杏仁核的特定区域表达最高。在依赖动物中和停药期间，皮质或海马中Srd5a1表达没有变化，这与我们最近在解剖组织中的发现不同。这些结果表明，WSP脑中的局部Srd5a1 mRNA表达可能不会与局部ALLO含量或戒断严重性平行变化。

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