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催化素-1/催化素受体1 调节神经可塑性和认知功能通过海马乳酸盐平衡在抑郁的模型中

Bing Chen¹, Kangyu Jin¹, Jingyi Dong¹

¹Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|August 9, 2024

概括

大型抑郁症会损害认知功能,这与克列-1失调有关. 阻断低素受体1 (HCRTR1) 通过恢复乳酸生产和神经可塑性来改善认知功能.

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
精神病学是一个精神病学.

背景情况:

认知功能障碍是主要抑郁症 (MDD) 的持续症状.
失调的低分泌蛋白 (Hcrt) 调节与抑郁症有关,但其在认知障碍中的确切作用尚不清楚.
在慢性不可预测轻度应激 (CUMS) 模型中观察到Hcrt-1水平的增加.

研究的目的:

阐明抑郁症中克列-1和认知功能障碍之间的相关性.
为了研究Hcrt-1-介导认知障碍背后的分子机制.
探索向HCrt-1通路的治疗潜力.

主要方法:

使用慢性不可预测轻度压力 (CUMS) 的小鼠模型.
使用的HCRTR1抗剂.
在老鼠中进行了hypocretin-1的静脉内注射.
对星体细胞和神经元进行了体外研究.
采用了微PET-CT成像和基因淘汰技术.

主要成果:

在CUMS小鼠中,高克列-1水平与通过HIF-1α减少的乳酸盐生产和BDNF表达相关.
这导致成人海马神经可塑性受损和认知缺陷.
HCRTR1抗剂可以逆转这些有害影响.
在老鼠中,直接给药催素-1 损害了认知行为和乳酸生产.
河马星球细胞中HCRTR1的淘汰模仿了这些认知和分子变化.

结论:

通过HCRTR1起作用的Hypocretin-1显著导致抑郁症的认知功能障碍.
Hcrt-1-HCRTR1通路影响海马乳酸的产生和神经可塑性.
准HCRTR1为与抑郁症相关的认知障碍提供了潜在的治疗策略.

关键词:

认知认知认知抑郁抑郁症抑郁症抑郁症是一种催產素-1‐1 的使用.缺氧诱导因子-1α.乳酸乳酸是一种乳酸.

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