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衰老或慢性压力会损害工作记忆,并调节前皮质皮质的GABA和谷氨酸基因表达

Hannah M Gandy¹, Fiona Hollis^1,2, Caesar M Hernandez^3,4

¹Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, SC, United States.

Frontiers in aging neuroscience

|January 23, 2024

概括

衰老和慢性压力会通过改变前额叶皮层 (PFC) 中的基因表达来损害工作记忆. 老化和压力都会影响谷氨酸和GABA信号通路,但通过不同的分子机制,表明独特的神经生物学变化.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
衰老研究研究衰老研究

背景情况:

葡萄糖皮质醇 (GC) 假说将压力,衰老和认知衰退联系在一起.
前额叶皮质 (PFC) 对工作记忆至关重要,受到压力和衰老的影响.
有限的研究已经探索了GC假设与PFC衰老和工作记忆有关.

研究的目的:

为了比较正常衰老和慢性变压 (CVS) 对PFC依赖工作记忆的影响.
研究老化和CVS下的PFC中谷氨酸和GABA信号基因的分子变化.
在PFC衰老和工作记忆的背景下评估GC假设的有效性.

主要方法:

使用操作器延迟匹配样本任务进行行为测试,以评估雄性F344大鼠的工作记忆.
在PFC的前临界 (PrL) 和下临界子区域的基因表达的分子分析.
在正常年龄老鼠和暴露于CVS的老鼠之间比较基因表达特征.

主要成果:

正常衰老和CVS都显著损害了工作记忆的准确性和性能.
正常的衰老会增加PrL中的GABA输送基因Slc6a11的表达.
在PrL中,CVS增加了谷蛋白质突触基因 (Grin2b,Grm4,Plcb1) 的表达.
在PrL中发现了衰老和CVS分子表型之间的积极关联,但不是下边膜亚区域.

结论:

PFC依赖的工作记忆和基因表达对衰老和慢性压力相对敏感,支持GC假设.
衰老和CVS诱导PFC中明显的分子变化,衰老影响GABA调节,CVS影响谷氨酸信号传递.
这些明显的变化表明,在衰老和慢性压力期间,PFC内抑制和激发信号的独特失衡.

关键词:

对于GABA来说,这是一个很好的选择.葡萄糖皮质类药物是什么谷氨酸酸盐的使用方法下垂体 - 下垂体 - 上腺轴这是正常的衰老过程.前额叶皮层前额叶皮层.心理压力是一种心理压力.

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