Role of mTOR-Regulated Autophagy in Synaptic Plasticity Related Proteins Downregulation and the Reference Memory Deficits Induced by Anesthesia/Surgery in Aged Mice
| العنوان: | Role of mTOR-Regulated Autophagy in Synaptic Plasticity Related Proteins Downregulation and the Reference Memory Deficits Induced by Anesthesia/Surgery in Aged Mice |
|---|---|
| المؤلفون: | Tao Xiaoyan, Siyu Zhang, Yunjian Ni, Weiwei Yan, Daqing Pei, Jian Lu, Sunan Gao, Shuai Kang, Hongmei Zhou |
| المصدر: | Frontiers in Aging Neuroscience Frontiers in Aging Neuroscience, Vol 13 (2021) |
| بيانات النشر: | Frontiers Media SA, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Aging, medicine.medical_specialty, Cognitive Neuroscience, Morris water navigation task, Hippocampus, Neurosciences. Biological psychiatry. Neuropsychiatry, 03 medical and health sciences, 0302 clinical medicine, Medicine, PI3K/AKT/mTOR pathway, Original Research, synaptic plasticity, biology, rapamycin, business.industry, postoperative cognitive dysfunction, Autophagy, medicine.disease, Surgery, aged, 030104 developmental biology, nervous system, Anesthesia, Synaptic plasticity, mTOR, Synaptophysin, biology.protein, business, Postoperative cognitive dysfunction, Postsynaptic density, 030217 neurology & neurosurgery, RC321-571, Neuroscience |
| الوصف: | Postoperative cognitive dysfunction increases mortality and morbidity in perioperative patients and has become a major concern for patients and caregivers. Previous studies demonstrated that synaptic plasticity is closely related to cognitive function, anesthesia and surgery inhibit synaptic function. In central nervous system, autophagy is vital to synaptic plasticity, homeostasis of synapticproteins, synapse elimination, spine pruning, proper axon guidance, and when dysregulated, is associated with behavioral and memory functions disorders. The mammalian target of rapamycin (mTOR) negatively regulates the process of autophagy. This study aimed to explore whether rapamycin can ameliorate anesthesia/surgery-induced cognitive deficits by inhibiting mTOR, activating autophagy and rising synaptic plasticity-related proteins in the hippocampus. Aged C57BL/6J mice were used to establish POCD models with exploratory laparotomy under isoflurane anesthesia. The Morris Water Maze (MWM) was used to measure reference memory after anesthesia and surgery. The levels of mTOR phosphorylation (p-mTOR), Beclin-1 and LC3-II were examined on postoperative days 1, 3 and 7 by western blotting. The levels of synaptophysin (SYN) and postsynaptic density protein 95 (PSD-95) in the hippocampus were also examined by western blotting. Here we showed that anesthesia/surgery impaired reference memory and induced the activation of mTOR, decreased the expression of autophagy-related proteins such as Beclin-1 and LC3-II. A corresponding decline in the expression of neuronal/synaptic, plasticity-related proteins such as SYN and PSD-95 was also observed. Pretreating mice with rapamycin inhibited the activation of mTOR and restored autophagy function, also increased the expression of SYN and PSD-95. Furthermore, anesthesia/surgery-induced learning and memory deficits were also reversed by rapamycin pretreatment. In conclusion, anesthesia/surgery induced mTOR hyperactivation and autophagy impairments, and then reduced the levels of SYN and PSD-95 in the hippocampus. An mTOR inhibitor, rapamycin, ameliorated anesthesia/surgery-related cognitive impairments by inhibiting the mTOR activity, inducing activation of autophagy, enhancing SYN and PSD-95 expression. |
| تدمد: | 1663-4365 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9d2b35a66de6908ac60630cc68cc1c81 https://doi.org/10.3389/fnagi.2021.628541 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9d2b35a66de6908ac60630cc68cc1c81 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16634365 |
|---|