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首页> 外文期刊>Frontiers in Cellular Neuroscience >Acute Ethanol Inhibition of γ Oscillations Is Mediated by Akt and GSK3β
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Acute Ethanol Inhibition of γ Oscillations Is Mediated by Akt and GSK3β

机译:Akt和GSK3β介导急性乙醇抑制γ振荡。

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摘要

Hippocampal network oscillations at gamma band frequency (γ, 30–80 Hz) are closely associated with higher brain functions such as learning and memory. Acute ethanol exposure at intoxicating concentrations (≥50 mM) impairs cognitive function. This study aimed to determine the effects and the mechanisms of acute ethanol exposure on γ oscillations in an in vitro model. Ethanol (25–100 mM) suppressed kainate-induced γ oscillations in CA3 area of the rat hippocampal slices, in a concentration-dependent, reversible manner. The ethanol-induced suppression was reduced by the D1R antagonist SCH23390 or the PKA inhibitor H89, was prevented by the Akt inhibitor triciribine or the GSk3β inhibitor SB415286, was enhanced by the NMDA receptor antagonist D-AP5, but was not affected by the MAPK inhibitor U0126 or PI3K inhibitor wortmanin. Our results indicate that the intracellular kinases Akt and GSk3β play a critical role in the ethanol-induced suppression of γ oscillations and reveal new cellular pathways involved in the ethanol-induced cognitive impairment.
机译:海马网络在γ频带频率(γ,30–80 Hz)处的振荡与较高的大脑功能(如学习和记忆)密切相关。醉人浓度(≥50mM)的急性乙醇暴露会损害认知功能。本研究旨在确定体外模型中急性乙醇暴露对γ振荡的影响及其机理。乙醇(25–100 mM)以浓度依赖性,可逆的方式抑制了海藻酸盐诱导的大鼠海马切片CA3区的γ振荡。 D1R拮抗剂SCH23390或PKA抑制剂H89降低了乙醇诱导的抑制作用,Akt抑制剂曲西立滨或GSk3β抑制剂SB415286阻止了乙醇诱导的抑制作用,NMDA受体拮抗剂D-AP5增强了乙醇诱导的抑制作用,但不受MAPK抑制剂影响U0126或PI3K抑制剂渥曼青霉素。我们的结果表明,细胞内激酶Akt和GSk3β在乙醇诱导的γ振荡抑制中起关键作用,并揭示了乙醇诱导的认知障碍所涉及的新细胞途径。

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