Connexin 43 contributes to perioperative neurocognitive disorder by attenuating perineuronal net of hippocampus in aged mice

作者：Qian Zhang, Yuxin Zhang, Peilin Cong, Qianqian Wu, Hanxi Wan, Xinwei Huang, Xinyang Li, Zhouxiang Li, Jingxuan Li, Huanghui Wu, Tian Li, Lize Xiong · 发表于：Cellular and Molecular Life Sciences · 年份：2025 · DOI：10.1007/s00018-024-05530-7 · 被引用次数：8 · 研究领域：Proteoglycans and glycosaminoglycans research、Connexins and lens biology、Intensive Care Unit Cognitive Disorders

BACKGROUND: Perioperative neurocognitive disorder (PND) is a prevalent form of cognitive impairment in elderly patients following anesthesia and surgery. The underlying mechanisms of PND are closely related to perineuronal nets (PNNs). PNNs, which are complexes of extracellular matrix primarily surrounding neurons in the hippocampus, play a critical role in neurocognitive function. Connexin 43 (Cx43) contributes to cognitive function by modulating the components of PNNs. This study was designed to investigate the specific regulatory mechanisms of Cx43 on PNNs and its pivotal role in the development of PND. METHODS: C57BL/6 mice were subjected to abdominal surgery under 1.4% isoflurane anesthesia. Cognitive functions, particularly learning and memory, were evaluated via the Y-maze test, Barnes maze (BM) and contextual fear conditioning test (CFT). The mRNA and protein expression levels of Cx43 were assessed by using quantitative reverse transcription polymerase chain reaction (qRT-PCR), fluorescent in situ hybridization (FISH), western blotting and flow cytometry. The quantity of PNNs was measured by Wisteria floribunda agglutinin (WFA) and Aggrecan staining. RESULTS: Aged mice subjected to anesthesia and surgery exhibited deficits in hippocampus-dependent cognitive functions, which were accompanied by increased Cx43 mRNA and protein expression. Conditional knockout (cKO) of Cx43 in astrocytes alleviated cognitive deficits and promoted the number of PNNs and dendritic spines i...