在老年小鼠中,progranulin 缺乏会通过RhoA介导的轴突损伤加剧术后认知功能障碍
Yini Lu1, Xinyu Tian2, Chun Yang3
1Department of Anesthesiology, Chongqing Health Center for Women and Children, Chongqing 401147, China; NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing 401147, China.
Brain research bulletin
|November 23, 2025
概括
进激素 (PGRN) 缺乏会通过RhoA.通过破坏神经元结构恶化术后认知功能障碍 (POCD). 恢复PGRN可以保护老年人免受POCD和认知衰退.
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
- 老年学是一门学科.
背景情况:
- 手术后认知功能障碍 (POCD) 是一种严重的并发症,特别是在老年手术患者中.
- 对POCD的潜在分子机制还没有完全了解.
- 这项研究探讨了progranulin (PGRN) 在海马神经元损伤和手术创伤后认知障碍中的作用.
研究的目的:
- 为了研究前列腺素 (PGRN) 对手术创伤引起的海马神经元损伤的影响.
- 阐明将PGRN与手术后认知障碍联系在一起的分子机制.
- 评估PGRN作为预防POCD的潜在治疗标.
主要方法:
- 老年小鼠接受了腹腔切除术以模拟POCD,通过行为测试评估认知功能.
- 用RNA测序来识别分子变化.
- 使用免疫光,戈尔吉染色和电子显微镜评估海马神经元完整性.
- 在体外实验中使用LPS治疗的HT22神经元与重组PGRN或RhoA操纵.
主要成果:
- 手术创伤降低了海马体PGRN表达,与轴突/树突损伤和认知衰退相关.
- 在实验室中,PGRN 缺乏会损害神经元外生长,而外源性PGRN 通过抑制RhoA而恢复神经元外生长.
- 过度表达RhoA抵消了PGRN的神经保护作用.
- 在体内给予PGRN可降低神经炎症,改善神经元功能,增强POCD小鼠的认知能力.
结论:
- PGRN 缺乏会通过RhoA介导的细胞骨功能障碍加剧POCD的发病.
- PGRN-RhoA通路是POCD的一个关键机制.
- 针对PGRN-RhoA轴提供了一种新的治疗策略,以保持神经元连接并减轻老化手术患者的认知衰退.
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