Astrocyte-microglia crosstalk in the hippocampus mediates cognitive impairments induced by chronic intermittent hypoxia

IF 5.6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Disease Pub Date : 2025-09-22 DOI:10.1016/j.nbd.2025.107117

Zhen-huan Wu , Ming-rui Zhai , Yu-rong Wang, Long Ren, Jie Pan, Lei Xiao, Yue-hua Liu

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引用次数: 0

Abstract

Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is a common systemic disease with a high-risk factor for developing cognitive impairment. However, the possible mechanism(s) underlying the cognitive function impairment in CIH remain largely unknown. In this study, our results reveal that 8-week CIH reliably induces significant cognitive impairment, synaptic deficits, and pronounced microglial activation characterized by excessive synaptic phagocytosis. Pharmacological depletion of microglia using PLX5622 ameliorated these CIH-induced impairments. Furthermore, CIH enhanced the interaction between activated astrocytes and microglia, accompanied by upregulation of complement C3 in astrocytes and C3aR in microglia. Notably, blocking C3aR with SB290157 attenuated microglial overactivation, reduced aberrant synaptic engulfment, and improved cognitive performance in CIH-exposed mice. Collectively, these findings demonstrate that C3/C3aR-mediated astrocyte-microglia crosstalk contributes to CIH-induced cognitive dysfunction by activating microglia to excessive phagocytosis of synapses.

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海马星形胶质细胞-小胶质细胞串扰介导慢性间歇性缺氧引起的认知障碍。

阻塞性睡眠呼吸暂停（OSA）是一种常见的全身性疾病，以慢性间歇性缺氧（CIH）为特征，是发生认知障碍的高危因素。然而，CIH中认知功能损害的可能机制在很大程度上仍然未知。在这项研究中，我们的研究结果显示，8周的CIH确实会引起显著的认知障碍、突触缺陷和明显的小胶质细胞激活，其特征是突触吞噬过度。使用PLX5622对小胶质细胞进行药理学耗竭可改善这些cih诱导的损伤。此外，CIH增强了活化的星形胶质细胞与小胶质细胞之间的相互作用，并伴有星形胶质细胞中补体C3和小胶质细胞中C3aR的上调。值得注意的是，用SB290157阻断C3aR可减轻cih暴露小鼠的小胶质细胞过度激活，减少异常突触吞噬，并改善认知表现。总之，这些发现表明C3/ c3ar介导的星形胶质细胞-小胶质细胞串扰通过激活小胶质细胞过度吞噬突触而导致cih诱导的认知功能障碍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.