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针刺通过调控小胶质细胞 PI3K 通路的表观遗传修饰改善创伤后应激障碍模型大鼠的学习记忆能力。

Acupuncture improves learning and memory ability of posttraumatic stress disorder model rats through epigenetic regulation of microglial phosphatidylinositol 3-kinase pathway.

机构信息

College of Traditional Chinese Medicine, Hainan Medical University, Haikou, Hainan, China.

College of Acupuncture-Moxibustion and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.

出版信息

Technol Health Care. 2023;31(S1):409-421. doi: 10.3233/THC-236035.

Abstract

BACKGROUND

Microglia express phosphatidylinositol 3-kinase (PI3K) has been implicated in the induction and maintenance of long-term potentiation (LTP) and in hippocampal synaptic plasticity. However, there are few studies on the interference of PI3K signal pathway in microglia.

OBJECTIVE

The study goal is to gain a better understanding of the mechanism by which EA affects synapses provides insights into how electroacupuncture (EA) modulates synaptic plasticity in learning and memory.

METHODS

Rat models of posttraumatic stress disorder (PTSD) were used to explore the effects of EA on microglial PI3K pathway, brain-derived neurotrophic factor (BDNF) and LTP, and the target and mechanism underlying the effects of EA on PI3K from the perspective of protein ubiquitination.

RESULTS

EA induced microglial BDNF expression by activating the PI3K-AKT pathway, thereby facilitating LTP and synaptic plasticity. EA inhibited lincRNA 02023 to rescue the binding of WWP2 to PTEN, thereby promoting PTEN ubiquitination and degradation.

CONCLUSION

The mechanism of EA improving the learning and memory ability of PTSD rats may be that it can promote the competitive combination of WWP2 and PTEN by inhibiting Linc RNA02023, and then lead to microglial PI3K and its pathway activation, BDNF up-regulation, and finally induce LTP and repair damaged synaptic plasticity.

摘要

背景

小胶质细胞表达的磷酸肌醇 3-激酶(PI3K)已被牵连在长时程增强(LTP)的诱导和维持以及海马突触可塑性中。然而,关于小胶质细胞中 PI3K 信号通路的干扰的研究较少。

目的

本研究旨在深入了解 EA 影响突触的机制,为电针(EA)如何调节学习和记忆中的突触可塑性提供思路。

方法

使用创伤后应激障碍(PTSD)大鼠模型,从蛋白质泛素化的角度探讨 EA 对小胶质细胞 PI3K 通路、脑源性神经营养因子(BDNF)和 LTP 的影响,以及 EA 对 PI3K 影响的靶点和机制。

结果

EA 通过激活 PI3K-AKT 通路诱导小胶质细胞 BDNF 表达,从而促进 LTP 和突触可塑性。EA 抑制 lincRNA 02023 以挽救 WWP2 与 PTEN 的结合,从而促进 PTEN 泛素化和降解。

结论

EA 改善 PTSD 大鼠学习记忆能力的机制可能是通过抑制 Linc RNA02023,促进 WWP2 和 PTEN 的竞争性结合,进而导致小胶质细胞 PI3K 及其通路的激活、BDNF 的上调,最终诱导 LTP 和修复受损的突触可塑性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce4/10200193/6bb779cf28d0/thc-31-thc236035-g001.jpg

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