Connexin 43 gap junction-mediated astrocytic network reconstruction attenuates isoflurane-induced cognitive dysfunction in mice

• DOI: 10.1186/s12974-022-02424-y
• Publication Date: 2022-03-07T15:02:46Z
• Authors: Rui Dong; Yuqiang Han; Linhao Jiang; Shuai Liu; Fujun Zhang; Liangyu Peng; Zimo Wang; Zhengliang Ma; Tianjiao Xia; Xiaoping Gu
• Keywords: Lucifer yellow

Postoperative cognitive dysfunction (POCD) is a common complication following anesthesia and surgery. General anesthetic isoflurane has potential neurotoxicity induces impairments, but the exact mechanism remains unclear. Astrocytes form interconnected networks in adult brain through gap junctions (GJs), which primarily comprise connexin 43 (Cx43), play important roles homeostasis functions such as memory. However, role of GJ-Cx43-mediated astrocytic network isoflurane-induced not been defined.4-month-old male C57BL/6 mice were exposure to long-term induce impairment. To simulate an vitro dysfunction-like condition, primary mouse astrocytes subjected exposure. Cognitive function was assessed by Y-maze fear conditioning tests. Western blot used determine expression levels different functional configurations Cx43. The morphology GJs-Cx43 evaluated immunofluorescence staining. Levels IL-1β IL-6 examined ELISA. ability GJs-Cx43-mediated intercellular communication lucifer yellow dye transfer assay. Ethidium bromide uptake assays measure activity Cx43 hemichannels. ultrastructural astrocyte tripartite synapse observed transmission electron microscopy.After anesthesia, GJs formed hippocampus significantly reduced, impaired, hemichannel enhanced, increased, showed significant After treatment with novel GJ-Cx43 enhancer ZP1609, neuroinflammation alleviated, ameliorated cognition induced ZP1609 enhances promoting without affecting activity. Additionally, our data that does alter structure synapse.Our results reveal involved provides new mechanistic insight into pathogenesis POCD identifies targets for its treatment.