核糖体失调:一种在人类抑郁症和小鼠慢性压力中保存的病理生理机制
Xiaolu Zhang1, Mahmoud Ali Eladawi2, William George Ryan2
1Department of Microbiology and Immunology, Louisiana State University Health Sciences Centre, Shreveport, LA 71105, USA.
PNAS nexus
|October 12, 2023
概括
重度抑郁症 (MDD) 涉及核糖体蛋白基因 (RPG) 下调和伪基因上调,是一种保存的应激反应. 这种核糖体失调会影响突触功能,导致情绪障碍异质性.
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
- 遗传学 是一个遗传学.
背景情况:
- 大型抑郁症 (MDD) 呈现的异质性使理解和治疗变得复杂.
- 在MDD的动物压力模型和临床观察之间存在差距.
- 驱动MDD变异性的生物机制尚不清楚.
研究的目的:
- 为了确定MDD和慢性压力背后的保存的分子机制.
- 调查核糖体蛋白基因 (RPGs) 在MDD和压力反应中的作用.
- 弥合慢性变压 (CVS) 和人类MDD的动物模型之间的差距.
主要方法:
- 对死后MDD脑组织和暴露于CVS的小鼠脑组织进行比较的转录组分析.
- 种子基因共同表达分析侧重于差异表达的RPGs.
- 在体外和体内分析以调查调节机制和治疗反应.
主要成果:
- 在MDD受试者和CVS小鼠中观察到RPGs的下调和RP伪基因的上调.
- 改变的RPG被发现通过RP-伪基驱动的机制来稳定地调节突触变化.
- RPG失调是一种葡萄糖皮质激素介导的内分泌应激反应,在MDD缓解期间逆转,对氨酸有反应.
结论:
- 核糖体失调代表了人类MDD和慢性压力中保存的表型.
- 压力引起的RPG和核糖体的改变有助于情绪障碍中的突触失调.
- 核糖体异质性可能解释抑郁症和其他情绪障碍的可变表现.
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