mTOR‐mediated autophagy in the hippocampus is involved in perioperative neurocognitive disorders in diabetic rats

• DOI: 10.1111/cns.13762
• Publication Date: 2021-11-16T17:56:13Z
• Authors: Xiaohui Chen; Fei Gao; Cuicui Lin; Andi Chen; Jianhui Deng; Pinzhong Chen; Mingxue Lin; Bingxin Xie; Yanling Liao; Cansheng Gong; Xiaochun Zheng
• Keywords: Sirolimus

Abstract Introduction Perioperative neurocognitive disorders (PND) are common neurological complications after surgery. Diabetes mellitus (DM) has been reported to be an independent risk factor for PND, but little is known about its mechanism of action. Mammalian target rapamycin (mTOR) signaling crucial neuronal growth, development, apoptosis, and autophagy, the dysregulation mTOR leads disorders. The present study investigated whether can attenuate PND by inhibiting activating autophagy in diabetic rats. Methods Male Sprague‐Dawley rats underwent tibial fracture surgery under isoflurane anesthesia establish a model. Cognitive functions were examined using Morris water maze test. levels phosphorylated (p‐mTOR), tau (p‐tau), autophagy‐related proteins (Beclin‐1, LC3), apoptosis‐related (Bax, Bcl‐2, cleaved caspase‐3) hippocampus on postoperative days 3, 7, 14 Western blot. Hippocampal amyloid β (Aβ) immunohistochemistry. Results data showed that surgical trauma and/or DM impaired cognitive function, induced activation, decreased Beclin‐1 LC3‐II/I ratio. Aβ p‐tau hippocampal apoptotic responses significantly higher or surgery‐treated than control further increased subjected Pretreatment with inhibited hyperactivation restored autophagic effectively decreasing hyperphosphorylation, deposition, apoptosis hippocampus. Furthermore, trauma‐induced also reversed pretreatment rapamycin. Conclusion results demonstrate regulates playing critical role underlying reveal modulation could promising therapeutic strategy patients diabetes.