由CHOP介导的海马突触可塑性和神经活动的破坏有助于慢性疼痛相关的认知缺陷
Qingsheng Meng1, Songxue Su1, Lei Lei2,3
1Department of Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
CNS neuroscience & therapeutics
|January 16, 2025
概括
慢性缩性神经损伤会导致细胞内膜网膜应激和C/EBP同源蛋白 (CHOP) 的上调,导致慢性疼痛和认知缺陷. 减少CHOP和ER压力可以改善突触可塑性和神经元活动.
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
- 病理学 病理学 病理学
背景情况:
- 细胞内膜网膜 (ER) 应激和随后的蛋白质平衡中断与神经退行性疾病有关.
- C/EBP同源蛋白 (CHOP) 是展开蛋白质反应 (UPR) 的一个关键生物标志物.
研究的目的:
- 调查CHOP在慢性疼痛和慢性缩性神经损伤 (CCI) 后认知障碍中的作用.
- 在CCI引起的神经缺陷的背景下,评估CHOP作为UPR的生物标志物.
主要方法:
- 莫里斯水迷宫和恐惧调节测试评估了记忆力. 量化了包括CHOP在内的ER压力标志物.
- 使用TUNEL测量了亡,并切割了caspase-3. 通过Golgi-Cox染色和长期强化 (LTP) 来评估突触可塑性.
- 通过免疫光和纤维光度测量来监测神经元活动. 使用LV-Ddit3-shRNAs击败了CHOP,并使用4-酸 (4-PBA) 缓解了ER压力.
主要成果:
- CCI引发了持续的疼痛和认知缺陷,伴随着ER扩张,CHOP上调,减少树突脊柱密度,以及背部CA1 (dCA1) 区域的LTP受损.
- 在CCI后,CaMKIIα/c-Fos联合定位和CaMKIIα介导的信号减少. 激活CaMKIIα可以缓解认知障碍.
- 在CCI小鼠中,CHOP敲除和4-PBA治疗改善了突触可塑性,神经元活动和认知功能.
结论:
- 在dCA1区域中CCI诱导的CHOP上调会损害突触可塑性和神经元活动.
- 这种障碍有助于与慢性疼痛相关的认知缺陷.
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