Activation of astrocyte Gq pathway in hippocampal CA1 region attenuates anesthesia/surgery induced cognitive dysfunction in aged mice
The elderly are particularly vulnerable to brain dysfunction after fracture surgery, but the mechanism underlying the cognitive decline due to anesthesia/surgery is not well understood. In this study, we observed hippocampus-dependent cognitive impairment in aged mice undergoing anesthesia and tibia...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.1040569/full |
| _version_ | 1811318546718785536 |
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| author | Xupeng Wang Yanan Li Juan Zhao Jiaxu Yu Qi Zhang Qi Zhang Fang Xu Yahui Zhang Qi Zhou Chunping Yin Zhiyong Hou Zhiyong Hou Qiujun Wang |
| author_facet | Xupeng Wang Yanan Li Juan Zhao Jiaxu Yu Qi Zhang Qi Zhang Fang Xu Yahui Zhang Qi Zhou Chunping Yin Zhiyong Hou Zhiyong Hou Qiujun Wang |
| author_sort | Xupeng Wang |
| collection | DOAJ |
| description | The elderly are particularly vulnerable to brain dysfunction after fracture surgery, but the mechanism underlying the cognitive decline due to anesthesia/surgery is not well understood. In this study, we observed hippocampus-dependent cognitive impairment in aged mice undergoing anesthesia and tibial fracture surgery, a common model of postoperative cognitive dysfunction in aged mice. We used Golgi staining and neuroelectrophysiological techniques to detect structurally and functionally impaired synaptic plasticity in hippocampal CA1 region of Postoperative cognitive dysfunction aged mice, respectively. Based on the ‘third party synapse’ hypothesis of astrocytes, we used glial fibrillary acidic protein to label astrocytes and found an increase in abnormal activation of astrocytes in the CA1 region of hippocampus. We hypothesize that abnormal astrocyte function is the driving force for impaired synaptic plasticity. So we used chemogenetic methods to intervene astrocytes. Injection of adeno-associated virus into the CA1 region of the hippocampus bilateral to aged mice resulted in the specific expression of the Gq receptor, a receptor specially designed to be activated only by certain drugs, within astrocytes. The results of novel object recognition and conditioned fear experiments showed that CNO activation of astrocyte Gq pathway could improve the learning and memory ability and the synaptic plasticity of Postoperative cognitive dysfunction aged mice was also improved. The results of this study suggest that activation of the Gq pathway in astrocytes alleviates Postoperative cognitive dysfunction induced by anesthesia and surgery in aged mice. |
| first_indexed | 2024-04-13T12:27:46Z |
| format | Article |
| id | doaj.art-35239ace43af47c38b0acd43daa6efcb |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-13T12:27:46Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-35239ace43af47c38b0acd43daa6efcb2022-12-22T02:46:58ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-11-011410.3389/fnagi.2022.10405691040569Activation of astrocyte Gq pathway in hippocampal CA1 region attenuates anesthesia/surgery induced cognitive dysfunction in aged miceXupeng Wang0Yanan Li1Juan Zhao2Jiaxu Yu3Qi Zhang4Qi Zhang5Fang Xu6Yahui Zhang7Qi Zhou8Chunping Yin9Zhiyong Hou10Zhiyong Hou11Qiujun Wang12Department of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaTeaching Experiment Center, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Anesthesiology, Hebei Children’s Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaNHC Key Laboratory of Intelligent Orthopaedic Equipment, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaThe elderly are particularly vulnerable to brain dysfunction after fracture surgery, but the mechanism underlying the cognitive decline due to anesthesia/surgery is not well understood. In this study, we observed hippocampus-dependent cognitive impairment in aged mice undergoing anesthesia and tibial fracture surgery, a common model of postoperative cognitive dysfunction in aged mice. We used Golgi staining and neuroelectrophysiological techniques to detect structurally and functionally impaired synaptic plasticity in hippocampal CA1 region of Postoperative cognitive dysfunction aged mice, respectively. Based on the ‘third party synapse’ hypothesis of astrocytes, we used glial fibrillary acidic protein to label astrocytes and found an increase in abnormal activation of astrocytes in the CA1 region of hippocampus. We hypothesize that abnormal astrocyte function is the driving force for impaired synaptic plasticity. So we used chemogenetic methods to intervene astrocytes. Injection of adeno-associated virus into the CA1 region of the hippocampus bilateral to aged mice resulted in the specific expression of the Gq receptor, a receptor specially designed to be activated only by certain drugs, within astrocytes. The results of novel object recognition and conditioned fear experiments showed that CNO activation of astrocyte Gq pathway could improve the learning and memory ability and the synaptic plasticity of Postoperative cognitive dysfunction aged mice was also improved. The results of this study suggest that activation of the Gq pathway in astrocytes alleviates Postoperative cognitive dysfunction induced by anesthesia and surgery in aged mice.https://www.frontiersin.org/articles/10.3389/fnagi.2022.1040569/fullPOCDastrocytesynaptic plasticitychemical geneticsaged mice |
| spellingShingle | Xupeng Wang Yanan Li Juan Zhao Jiaxu Yu Qi Zhang Qi Zhang Fang Xu Yahui Zhang Qi Zhou Chunping Yin Zhiyong Hou Zhiyong Hou Qiujun Wang Activation of astrocyte Gq pathway in hippocampal CA1 region attenuates anesthesia/surgery induced cognitive dysfunction in aged mice Frontiers in Aging Neuroscience POCD astrocyte synaptic plasticity chemical genetics aged mice |
| title | Activation of astrocyte Gq pathway in hippocampal CA1 region attenuates anesthesia/surgery induced cognitive dysfunction in aged mice |
| title_full | Activation of astrocyte Gq pathway in hippocampal CA1 region attenuates anesthesia/surgery induced cognitive dysfunction in aged mice |
| title_fullStr | Activation of astrocyte Gq pathway in hippocampal CA1 region attenuates anesthesia/surgery induced cognitive dysfunction in aged mice |
| title_full_unstemmed | Activation of astrocyte Gq pathway in hippocampal CA1 region attenuates anesthesia/surgery induced cognitive dysfunction in aged mice |
| title_short | Activation of astrocyte Gq pathway in hippocampal CA1 region attenuates anesthesia/surgery induced cognitive dysfunction in aged mice |
| title_sort | activation of astrocyte gq pathway in hippocampal ca1 region attenuates anesthesia surgery induced cognitive dysfunction in aged mice |
| topic | POCD astrocyte synaptic plasticity chemical genetics aged mice |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.1040569/full |
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