Exercise-conditioned plasma ameliorates postoperative cognitive dysfunction by activating hippocampal cholinergic circuit and enhancing BDNF/TrkB signaling

作者：Xiaodi Lu, Weijie Xiong, Zhuo Chen, Y. Li, Fengyan Xu, Xue Yang, Melissa Long, Wenhan Guo, Shuliang Wu, Liang Sun, Guonian Wang · 发表于：Cell Communication and Signaling · 年份：2024 · DOI：10.1186/s12964-024-01938-7 · 被引用次数：24 · 研究领域：Intensive Care Unit Cognitive Disorders、Enhanced Recovery After Surgery、Traumatic Brain Injury and Neurovascular Disturbances

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a prevalent complication following anesthesia and surgery, particularly in the elderly, leading to increased mortality and reduced quality of life. Despite its prevalence, there are no effective clinical treatments. Exercise has shown cognitive benefits in aging and various diseases, which can be transferred to sedentary animals through plasma. However, it is unclear if exercise-conditioned plasma can replicate these benefits in the context of POCD. METHODS: Sixteen-month-old male C57BL/6J mice underwent 30 days of voluntary running wheel training or received systemic administration of exercise-conditioned plasma, followed by tibial fracture surgery under general anesthesia at 17 months of age. Cognitive performance, hippocampal synaptic deficits, neuroinflammation, BDNF/TrkB signaling, and medial septum (MS)-hippocampal cholinergic activity were evaluated through immunohistochemical staining, transmission electron microscopy, Western blotting, and biochemical assays. To investigate the role of hippocampal BDNF signaling and cholinergic activity in the therapeutic effects, the TrkB antagonist ANA-12 and the cholinergic receptor muscarinic 1 (CHRM1) antagonist trihexyphenidyl (THP) were administered via intraperitoneal injection, and adeno-associated virus (AAV) vectors expressing Chrm1 shRNA were delivered via intrahippocampal stereotaxic microinjection. RESULTS: Exercise-conditioned plasma mimicked the benefits of exe...