药物开发 药物开发
Giulio Maria Pasinetti1,2, Eun-Jeong Yang1,3, Nicole Less4
1Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 26, 2025
概括
容易受到压力会加速阿尔茨海默氏症患者的认知衰退.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 遗传学 遗传学 是一个
背景情况:
- 早期抑郁症与阿尔茨海默病 (AD) 风险增加有关.
- 适应不良应激反应在阿尔茨海默病发病和进展中的作用仍然不清楚.
- 这项研究调查了应激易感性作为AD的潜在风险因素.
研究的目的:
- 在小鼠模型中测试压力易感性是否促进认知恶化和AD神经病理.
- 为了确定AD模型小鼠与野生类型对照中的不同应激敏感性.
- 探索AD中压力诱导的认知变化背后的分子机制.
主要方法:
- 在8周大的5xFAD (AD模型) 和WT小鼠中利用了慢性社会失败压力 (RSDS) 范式.
- 通过行为测试评估压力易感性/弹性 (焦虑/抑郁类行为,新型物体识别).
- 使用CyTOF进行免疫细胞分析和海马的RNA测序,用CIBERSORTx和IPA进行分析.
主要成果:
- 11周大的5xFAD小鼠与WT小鼠 (39.4%) 相比,表现出更高的压力易感性 (61.2%).
- 敏感的5xFAD小鼠,但不是弹性小鼠,与未经压力5xFAD小鼠相比,表现出加速的认知障碍.
- 认知障碍易感的5xFAD小鼠表现出与突触可塑性相关的海马体基因表达的改变.
结论:
- 在AD小鼠模型中,压力易感性是认知衰退的重要因素.
- 突出了AD中压力反应的异质性.
- 要求对阿尔茨海默病发病过程中的应激反应机制进行进一步的研究.
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