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急性和慢性电惊厥发作对大鼠脑中G蛋白信号调节因子mRNA表达的调控

Regulation of regulators of G protein signaling mRNA expression in rat brain by acute and chronic electroconvulsive seizures.

作者信息

Gold Stephen J, Heifets Boris D, Pudiak Cindy M, Potts Bryan W, Nestler Eric J

机构信息

Department of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center at Dallas, Texas 75390, USA.

出版信息

J Neurochem. 2002 Aug;82(4):828-38. doi: 10.1046/j.1471-4159.2002.01002.x.

Abstract

G protein-coupled receptor (GPCR) signaling cascades may be key substrates for the antidepressant effects of chronic electroconvulsive seizures (ECS). To better understand changes in these signaling pathways, alterations in levels of mRNA's encoding regulators of G protein signaling (RGS) protein subtypes-2, -4, -7, -8 and -10 were evaluated in rat brain using northern blotting and in situ hybridization. In prefrontal cortex, RGS2 mRNA levels were increased several-fold 2 h following an acute ECS. Increases in RGS8 mRNA were of lesser magnitude (30%), and no changes were evident for the other RGS subtypes. At 24 h following a chronic ECS regimen, RGS4, -7, and -10 mRNA levels were reduced by 20-30%; only RGS10 was significantly reduced 24 h after acute ECS. Levels of RGS2 mRNA were unchanged 24 h following either acute or chronic ECS. In hippocampus, RGS2 mRNA levels were markedly increased 2 h following acute ECS. More modest increases were seen for RGS4 mRNA expression, whereas levels of the other RGS subtypes were unaltered. At 24 h following chronic ECS, RGS7, -8 and -10 mRNA levels were decreased in the granule cell layer, and RGS7 and -8 mRNA levels were decreased in the pyramidal cell layers. Only RGS8 and -10 mRNA levels were significantly reduced in hippocampus 24 h following an acute ECS. Paralleling neocortex, RGS2 mRNA content was unchanged in hippocampus 24 h following either acute or chronic ECS. In ventromedial hypothalamus, RGS4 mRNA content was increased 24 h following chronic ECS, whereas RGS7 mRNA levels were only increased 24 h following an acute ECS. The increased RGS4 mRNA levels in hypothalamus were significant by 2 h following an acute ECS. These studies demonstrate subtype-, time-, and region-specific regulation of RGS proteins by ECS, adaptations that may contribute to the antidepressant effects of this treatment.

摘要

G蛋白偶联受体(GPCR)信号级联可能是慢性电惊厥发作(ECS)抗抑郁作用的关键底物。为了更好地理解这些信号通路的变化,我们使用Northern印迹法和原位杂交技术,评估了大鼠脑中编码G蛋白信号调节因子(RGS)蛋白亚型-2、-4、-7、-8和-10的mRNA水平的变化。在额叶前皮质,急性ECS后2小时,RGS2 mRNA水平增加了几倍。RGS8 mRNA的增加幅度较小(30%),其他RGS亚型则无明显变化。在慢性ECS方案后24小时,RGS4、-7和-10 mRNA水平降低了20-30%;急性ECS后24小时,只有RGS10显著降低。急性或慢性ECS后24小时,RGS2 mRNA水平均未改变。在海马体中,急性ECS后2小时,RGS2 mRNA水平显著增加。RGS4 mRNA表达有适度增加,而其他RGS亚型的水平未改变。慢性ECS后24小时,颗粒细胞层中RGS7、-8和-10 mRNA水平降低,锥体细胞层中RGS7和-8 mRNA水平降低。急性ECS后24小时,海马体中只有RGS8和-10 mRNA水平显著降低。与新皮质相似,急性或慢性ECS后24小时,海马体中RGS2 mRNA含量均未改变。在腹内侧下丘脑,慢性ECS后24小时,RGS4 mRNA含量增加,而RGS7 mRNA水平仅在急性ECS后24小时增加。急性ECS后2小时,下丘脑RGS4 mRNA水平的增加就很显著。这些研究表明,ECS对RGS蛋白具有亚型、时间和区域特异性调节,这些适应性变化可能有助于这种治疗的抗抑郁作用。

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