Exercise-conditioned plasma ameliorates postoperative cognitive dysfunction by activating hippocampal cholinergic circuit and enhancing BDNF/TrkB signaling
Abstract 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...
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BMC
2024-11-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-024-01938-7 |
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| author | Xiaodi Lu Weijie Xiong Zhuo Chen Yurou Li Fengyan Xu Xue Yang Meiwen Long Wenhan Guo Shuliang Wu Liang Sun Guonian Wang |
| author_facet | Xiaodi Lu Weijie Xiong Zhuo Chen Yurou Li Fengyan Xu Xue Yang Meiwen Long Wenhan Guo Shuliang Wu Liang Sun Guonian Wang |
| author_sort | Xiaodi Lu |
| collection | DOAJ |
| description | Abstract 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 exercise, alleviating cognitive decline induced by anesthesia/surgery, restoring hippocampal synapse formation and levels of regulators for synaptic plasticity, inhibiting neuroinflammatory responses to surgery by microglia and astrocytes, augmenting BDNF production and TrkB phosphorylation in hippocampal neurons, astrocytes, and microglia, upregulating MS expression of choline acetyltransferase (CHAT) and hippocampal expression of CHRM1 in neurons and astrocytes, and enhancing hippocampal cholinergic innervation and acetylcholine release. Conversely, ANA-12 administration blocked TrkB activation and reduced the protective effects on cognition, synaptic deficits, and neuroinflammatory reactivity of glial cells post-surgery. Similarly, THP administration or intrahippocampal delivery of AAV-Chrm1 shRNA inhibited the activation of the hippocampal cholinergic circuit by exercise plasma, negating the cognitive and neuropathological benefits and reducing BDNF/TrkB signaling enhancements. Conclusion Exercise-conditioned plasma can replicate the protective effects of exercise against anesthesia/surgery-induced neuroinflammation, synaptic, and cognitive impairments, at least partly, through CHRM1-dependent regulation of hippocampal cholinergic activity and BDNF/TrkB signaling. |
| format | Article |
| id | doaj-art-2e7bfad2d0ea417a8f3189a3f19d6f0f |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
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| series | Cell Communication and Signaling |
| spelling | doaj-art-2e7bfad2d0ea417a8f3189a3f19d6f0f2024-11-24T12:36:16ZengBMCCell Communication and Signaling1478-811X2024-11-0122113010.1186/s12964-024-01938-7Exercise-conditioned plasma ameliorates postoperative cognitive dysfunction by activating hippocampal cholinergic circuit and enhancing BDNF/TrkB signalingXiaodi Lu0Weijie Xiong1Zhuo Chen2Yurou Li3Fengyan Xu4Xue Yang5Meiwen Long6Wenhan Guo7Shuliang Wu8Liang Sun9Guonian Wang10Department of Anesthesiology, Harbin Medical University Cancer HospitalDepartment of Human Anatomy, School of Basic Medicine, Harbin Medical UniversityDepartment of Anesthesiology, Harbin Medical University Cancer HospitalDepartment of Human Anatomy, School of Basic Medicine, Harbin Medical UniversityDepartment of Human Anatomy, School of Basic Medicine, Harbin Medical UniversityDepartment of Human Anatomy, School of Basic Medicine, Harbin Medical UniversityDepartment of Human Anatomy, School of Basic Medicine, Harbin Medical UniversityDepartment of Human Anatomy, School of Basic Medicine, Harbin Medical UniversityDepartment of Human Anatomy, School of Basic Medicine, Harbin Medical UniversityDepartment of Human Anatomy, School of Basic Medicine, Harbin Medical UniversityDepartment of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical UniversityAbstract 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 exercise, alleviating cognitive decline induced by anesthesia/surgery, restoring hippocampal synapse formation and levels of regulators for synaptic plasticity, inhibiting neuroinflammatory responses to surgery by microglia and astrocytes, augmenting BDNF production and TrkB phosphorylation in hippocampal neurons, astrocytes, and microglia, upregulating MS expression of choline acetyltransferase (CHAT) and hippocampal expression of CHRM1 in neurons and astrocytes, and enhancing hippocampal cholinergic innervation and acetylcholine release. Conversely, ANA-12 administration blocked TrkB activation and reduced the protective effects on cognition, synaptic deficits, and neuroinflammatory reactivity of glial cells post-surgery. Similarly, THP administration or intrahippocampal delivery of AAV-Chrm1 shRNA inhibited the activation of the hippocampal cholinergic circuit by exercise plasma, negating the cognitive and neuropathological benefits and reducing BDNF/TrkB signaling enhancements. Conclusion Exercise-conditioned plasma can replicate the protective effects of exercise against anesthesia/surgery-induced neuroinflammation, synaptic, and cognitive impairments, at least partly, through CHRM1-dependent regulation of hippocampal cholinergic activity and BDNF/TrkB signaling.https://doi.org/10.1186/s12964-024-01938-7POCDExercisePlasmaCholinergic circuitBDNF/TrkB |
| spellingShingle | Xiaodi Lu Weijie Xiong Zhuo Chen Yurou Li Fengyan Xu Xue Yang Meiwen Long Wenhan Guo Shuliang Wu Liang Sun Guonian Wang Exercise-conditioned plasma ameliorates postoperative cognitive dysfunction by activating hippocampal cholinergic circuit and enhancing BDNF/TrkB signaling Cell Communication and Signaling POCD Exercise Plasma Cholinergic circuit BDNF/TrkB |
| title | Exercise-conditioned plasma ameliorates postoperative cognitive dysfunction by activating hippocampal cholinergic circuit and enhancing BDNF/TrkB signaling |
| title_full | Exercise-conditioned plasma ameliorates postoperative cognitive dysfunction by activating hippocampal cholinergic circuit and enhancing BDNF/TrkB signaling |
| title_fullStr | Exercise-conditioned plasma ameliorates postoperative cognitive dysfunction by activating hippocampal cholinergic circuit and enhancing BDNF/TrkB signaling |
| title_full_unstemmed | Exercise-conditioned plasma ameliorates postoperative cognitive dysfunction by activating hippocampal cholinergic circuit and enhancing BDNF/TrkB signaling |
| title_short | Exercise-conditioned plasma ameliorates postoperative cognitive dysfunction by activating hippocampal cholinergic circuit and enhancing BDNF/TrkB signaling |
| title_sort | exercise conditioned plasma ameliorates postoperative cognitive dysfunction by activating hippocampal cholinergic circuit and enhancing bdnf trkb signaling |
| topic | POCD Exercise Plasma Cholinergic circuit BDNF/TrkB |
| url | https://doi.org/10.1186/s12964-024-01938-7 |
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