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牙状环中的TAAR1参与慢性压力诱导的海马体可塑性和认知功能的损伤

Yue Zhang¹, Xian-Qiang Zhang¹, Wei-Pan Niu¹

¹Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China.

Progress in neuro-psychopharmacology & biological psychiatry

|March 21, 2024

概括

牙状环中的微氨基关联受体1 (TAAR1) 对于减轻对记忆和神经发生的慢性压力影响至关重要. TAAR1激动剂显示出治疗与主要抑郁症 (MDD) 相关的认知缺陷的潜力.

科学领域:

神经科学是一个神经科学.
分子精神病学分子精神病学
行为神经科学行为神经科学

背景情况:

微氨基关联受体1 (TAAR1) 与严重抑郁症 (MDD) 等与压力相关的疾病有关.
转录基因数据表明TAAR1在成年人神经生成中的作用,但其在慢性压力下的牙状环中的功能尚未被探索.

研究的目的:

为了研究TAAR1在牙状回形 (DG) 中的作用,以调解慢性压力诱导对大鼠海马的可塑性和行为的影响.
评估TAAR1激动剂在慢性压力小鼠模型中的治疗潜力.

主要方法:

利用RNAscope,遗传淘汰模型,行为测试 (社会记忆,空间物体识别),免疫组织化学和戈尔吉-考克斯染色.
研究了慢性社会失败压力对TAAR1表达,神经发生和神经元形态学的影响.
评估了选择性TAAR1激动剂 (RO5263397) 对压力诱导的缺陷的影响.

主要成果:

慢性压力导致DG中TAAR1mRNA减少,社会和空间记忆受损,同时减少成人出生牙状颗粒细胞的增殖和成熟.
在GD中选择性淘汰TAAR1复制了压力诱导的认知和神经发生缺陷.
在暴露于压力中的RO5263397的使用改善了认知障碍,神经发生缺陷和DG神经元的结构变化.

结论:

总局的TAAR1在慢性压力下调节海马的可塑性和认知功能方面发挥着关键作用.
TAAR1激动剂代表了与MDD和其他与压力相关的疾病相关的认知障碍的有前途的治疗策略.

关键词:

成年人的神经发生.慢性压力是一种慢性压力.认知功能认知功能牙状转 (Dentate gyrus) 是一个牙状转.大型抑郁症主要是抑郁症.在TAAR1中,TAAR1是TAAR1.

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