首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Ethanol-induced changes in the expression of proteins related to neurotransmission and metabolism in different regions of the rat brain.
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Ethanol-induced changes in the expression of proteins related to neurotransmission and metabolism in different regions of the rat brain.

机译:乙醇诱导的大鼠大脑不同区域与神经传递和代谢相关的蛋白质表达变化。

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Despite extensive description of the damaging effects of chronic alcohol exposure on brain structure, mechanistic explanations for the observed changes are just emerging. To investigate regional brain changes in protein expression levels following chronic ethanol treatment, one rat per sibling pair of male Wistar rats was exposed to intermittent (14 h/day) vaporized ethanol, the other to air for 26 weeks. At the end of 24 weeks of vapor exposure, the ethanol group had blood ethanol levels averaging 450 mg%, had not experienced a protracted (> 16 h) withdrawal from ethanol, and revealed only mild evidence of hepatic steatosis. Extracted brains were micro-dissected to isolate the prefrontal cortex (PFC), dorsal striatum (STR), corpus callosum genu (CCg), CC body (CCb), anterior vermis (AV), and anterior dorsal lateral cerebellum (ADLC) for protein analysis with two-dimensional gel electrophoresis. Expression levels for 54 protein spots were significantly different between the ethanol- and air-treated groups. Of these 54 proteins, tandem mass spectroscopy successfully identified 39 unique proteins, the levels of which were modified by ethanol treatment: 13 in the PFC, 7 in the STR, 2 in the CCg, 7 in the CCb, 7 in the AV, and 5 in the ADLC. The functions of the proteins altered by chronic ethanol exposure were predominantly associated with neurotransmitter systems in the PFC and cell metabolism in the STR. Stress response proteins were elevated only in the PFC, AV, and ADLC perhaps supporting a role for frontocerebellar circuitry disruption in alcoholism. Of the remaining proteins, some had functions associated with cytoskeletal physiology (e.g., in the CCb) and others with transcription/translation (e.g., in the ADLC). Considered collectively, all but 4 of the 39 proteins identified in the present study have been previously identified in ethanol gene- and/or protein-expression studies lending support for their role in ethanol-related brain alterations.
机译:尽管广泛描述了慢性酒精暴露对大脑结构的破坏作用,但有关观察到的变化的机械解释仍在不断涌现。为了研究慢性乙醇治疗后大脑局部区域蛋白质表达水平的变化,每对同胞雄性Wistar大鼠中的一只大鼠暴露于间歇性(14小时/天)汽化乙醇中,另一只暴露于空气中26周。在暴露于蒸气的24周结束时,乙醇组的血液中乙醇水平平均为450 mg%,没有经历过长时间(> 16小时)退出乙醇,并且仅显示出轻度肝脂肪变性的证据。将提取的大脑进行显微解剖以分离前额叶皮层(PFC),背侧纹状体(STR),call体属(CCg),CC体(CCb),前ver(AV)和前背小脑外侧(ADLC)二维凝胶电泳分析。乙醇和空气处理组之间的54个蛋白斑点的表达水平显着不同。在这54种蛋白质中,串联质谱法成功鉴定出39种独特的蛋白质,这些蛋白质的水平已通过乙醇处理进行了修饰:PFC中的13种,STR中的7种,CCg中的2种,CCb中的7种,AV中的7种以及AV中的7种。 ADLC中的5。慢性乙醇暴露所改变的蛋白质功能主要与PFC中的神经递质系统和STR中的细胞代谢有关。应激反应蛋白仅在PFC,AV和ADLC中升高,可能支持酒精中毒的小脑前回路破坏。在其余的蛋白质中,一些具有与细胞骨架生理相关的功能(例如在CCb中),而其他具有转录/翻译的功能(例如在ADLC中)。综合考虑,本研究中鉴定的39种蛋白质中除4种以外的所有蛋白质,先前都已在乙醇基因和/或蛋白质表达研究中鉴定出来,这为它们在乙醇相关的大脑变化中的作用提供了支持。

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