ArticleCellular and molecular life sciences : CMLS2025
Connexin 43 contributes to perioperative neurocognitive disorder by attenuating perineuronal net of hippocampus in aged mice.
Article in Cellular and molecular life sciences : CMLS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- The Janus Face of Isoflurane: A Dose-Age-Response Model of Cognitive Impact.Biomolecules · 2026Review
- Advances in electroacupuncture for perioperative neurocognitive disorders: mechanisms and clinical evidence.Chinese medicine · 2026Review
- FADS1 contributes to anesthesia/surgery-induced cognitive impairment by aggravating omega-6 fatty acid metabolic disruption in aged mice.Journal of neuroinflammation · 2026Article
- Fermented Soybean Pulp Alleviates Disease Progression of 5×FAD Model Mice.Molecular neurobiology · 2025Article
- Role of transforming growth factorβ in neurovascular unit during cerebral small vessel disease.Fluids and barriers of the CNS · 2025Review
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12 authors.
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Abstract
backgroundPerioperative 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.
methodsEighteen-month-old wild-type and Gja1
resultsAged 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 in the hippocampus by targeting Dmp1. Knockdown of Dmp1 attenuated the beneficial effects of Cx43 cKO on cognitive deficits induced by anesthesia and surgery.
conclusionOur findings indicate that anesthesia and surgery induce an increase in Cx43 expression, which inhibits the formation of PNNs and dendritic spines in hippocampus by suppressing Dmp1 transcription, leading to cognitive deficits in aged mice. These results offer new mechanistic insights into the pathogenesis of PND and identify potential targets for therapeutic intervention.
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