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<p>Postoperative cognitive dysfunction (POCD) is common in elderly surgical patients, and it can prolong recovery time and affect the quality of life. Although esketamine has been reported to alleviate POCD, its specific mechanism is not yet fully understood. This study investigates the effects of esketamine on POCD and its underlying molecular mechanisms. After exploratory laparotomy under isoflurane anesthesia, aged mice were treated with 10&#xa0;mg/kg of esketamine via intraperitoneal injection. The findings of this study indicate that intraperitoneal administration of esketamine could alleviate POCD, as demonstrated through a suite of behavioral tests. Moreover, we collected hippocampal samples and used proteomics to obtain differentially expressed proteins, then cross-referenced them with the GO database to identify Rho-associated coiled-coil kinase 2 (Rock2) as a potential target molecule for esketamine to alleviate POCD. We further confirmed using Western blotting that esketamine downregulates the increase in Rock2 expression and the phosphorylation of the Ser726 site on alpha-adducin (S726-Add1) induced by anesthesia and surgery in aged mice. Furthermore, the damage to dendritic spine density, dendritic complexity, and synaptic plasticity in the hippocampal region caused by anesthesia and surgery showed improvement to a certain extent after esketamine treatment, as demonstrated by Golgi staining, transmission electron microscopy, and electrophysiological assessments. In summary, esketamine improved POCD in aged mice, indicating that its mechanism may involve the protection of synaptic plasticity through the Rock2/Add1 pathway. This research may provide new perspectives for the pharmacological treatment of POCD.</p>

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Esketamine Alleviates Postoperative Cognitive Dysfunction via Rock2/Add1 Signaling Pathway in Aged Mice

  • 期刊论文

  • 发表日期：

    2026年3月4日

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  • Chang Xu,
  • Yonghai Zhang,
  • Yao Liu,
  • Xiaoyun Niu,
  • Chanhua Zhang,
  • Na Zhao,
  • Yan Wu,
  • Hanxiang Ma,
  • Yujun Wen,
  • Xinli Ni

摘要

Postoperative cognitive dysfunction (POCD) is common in elderly surgical patients, and it can prolong recovery time and affect the quality of life. Although esketamine has been reported to alleviate POCD, its specific mechanism is not yet fully understood. This study investigates the effects of esketamine on POCD and its underlying molecular mechanisms. After exploratory laparotomy under isoflurane anesthesia, aged mice were treated with 10 mg/kg of esketamine via intraperitoneal injection. The findings of this study indicate that intraperitoneal administration of esketamine could alleviate POCD, as demonstrated through a suite of behavioral tests. Moreover, we collected hippocampal samples and used proteomics to obtain differentially expressed proteins, then cross-referenced them with the GO database to identify Rho-associated coiled-coil kinase 2 (Rock2) as a potential target molecule for esketamine to alleviate POCD. We further confirmed using Western blotting that esketamine downregulates the increase in Rock2 expression and the phosphorylation of the Ser726 site on alpha-adducin (S726-Add1) induced by anesthesia and surgery in aged mice. Furthermore, the damage to dendritic spine density, dendritic complexity, and synaptic plasticity in the hippocampal region caused by anesthesia and surgery showed improvement to a certain extent after esketamine treatment, as demonstrated by Golgi staining, transmission electron microscopy, and electrophysiological assessments. In summary, esketamine improved POCD in aged mice, indicating that its mechanism may involve the protection of synaptic plasticity through the Rock2/Add1 pathway. This research may provide new perspectives for the pharmacological treatment of POCD.