Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer’s Disease
Background: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by loss of recognition and memory. Neuroinflammation plays pivotal roles in the pathology of AD and affects the progression of the disease. Astrocyte and microglia, as main immune executors in the central nervous syste...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.689629/full |
| _version_ | 1818361856498073600 |
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| author | Lushuang Xie Lushuang Xie Yi Liu Ning Zhang Chenyu Li Aaron F. Sandhu Aaron F. Sandhu George Williams George Williams Yan Shen Hongying Li Qiaofeng Wu Qiaofeng Wu Shuguang Yu Shuguang Yu |
| author_facet | Lushuang Xie Lushuang Xie Yi Liu Ning Zhang Chenyu Li Aaron F. Sandhu Aaron F. Sandhu George Williams George Williams Yan Shen Hongying Li Qiaofeng Wu Qiaofeng Wu Shuguang Yu Shuguang Yu |
| author_sort | Lushuang Xie |
| collection | DOAJ |
| description | Background: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by loss of recognition and memory. Neuroinflammation plays pivotal roles in the pathology of AD and affects the progression of the disease. Astrocyte and microglia, as main immune executors in the central nervous system (CNS), participate into the inflammatory response in AD. Glia polarize into different phenotypes during neurodegeneration. Pro-inflammatory glia produce cytokines (IL-1β, TNF-α, and IL-6) resulting into debris aggregates and neurotoxicity. Anti-inflammatory phenotypes produce cytokines (IL-4 and IL-10) to release the inflammation. Electroacupuncture is a useful treatment that has been found to slow the neurodegeneration in animals through experimentation and in humans through clinical trials. The aim of this study was to uncover the mechanisms of glia activation, microglia polarization, and cytokine secretion regulated by electroacupuncture as a treatment for AD.Methods: Twenty male Sprague–Dawley (SD) rats were randomly divided into four groups: Control group (Control), Normal saline group (NS), AD group (AD), and Electroacupuncture group (Acupuncture). The AD and Acupuncture groups were bilaterally injected with Aβ1–42 into the CA1 field of the hippocampus. The Acupuncture group received electroacupuncture stimulation on the acupoint “Baihui” (GV20) for 6 days per week for a total of 3 weeks. The Morris Water Maze (MWM) was used to evaluate learning and memory capacity. Immunofluorescence was used to stain GFAP and Iba1 of the DG and CA1 in the hippocampus, which, respectively, expressed the activation of astrocyte and microglia. The M1 microglia marker, inducible nitric oxide synthase (iNOS), and M2 marker Arginase 1 (Arg1) were used to analyze the polarization of microglia. The pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), anti-inflammatory cytokines (IL-4 and IL-10), and pathway-molecules (p65 and Stat6) were tested to analyze the glia inflammatory response by immunofluorescence and polymerase chain reaction (PCR).Results: The MWM results showed that electroacupuncture improves the escape latency time and the swimming distance of AD rats. The number of GFAP and Iba1 cells significantly increased in AD rats, but electroacupuncture decreased the cells. The iNOS-positive cells were significantly increased in AD, and electroacupuncture decreased the positive cells. Electroacupuncture elevated Arg1-positive cells in AD rats. Electroacupuncture decreased the glia pro-inflammatory cytokine expression and increased the anti-inflammatory cytokine expression in AD rats. Furthermore, electroacupuncture inhibited the NF-κB pathway molecule (p65) while raising the Stat6 pathway molecule (Stat6).Conclusion: These results provide evidence that electroacupuncture improves the recognition abilities and memory of AD rats. Electroacupuncture inhibits the activation of glia and polarizes microglia toward the M2 phenotype. Electroacupuncture decreased the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) and increased the anti-inflammatory cytokines (IL-4 and IL-10). Furthermore, electroacupuncture affects the immune responses through inhibition of NF-κB pathway but activation of Stat6 pathway. |
| first_indexed | 2024-12-13T21:23:20Z |
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| last_indexed | 2024-12-13T21:23:20Z |
| publishDate | 2021-09-01 |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-f5c2df4889574a18973abc357070b84d2022-12-21T23:31:02ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-09-011510.3389/fnins.2021.689629689629Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer’s DiseaseLushuang Xie0Lushuang Xie1Yi Liu2Ning Zhang3Chenyu Li4Aaron F. Sandhu5Aaron F. Sandhu6George Williams7George Williams8Yan Shen9Hongying Li10Qiaofeng Wu11Qiaofeng Wu12Shuguang Yu13Shuguang Yu14College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaInstitute of Electroacupuncture and Homeostasis Regulation, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Neurology, Dalian Municipal Central Hospital, Affiliated Hospital of Dalian Medical University, Dalian, ChinaElectroacupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaElectroacupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesElectroacupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaElectroacupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaInstitute of Electroacupuncture and Homeostasis Regulation, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaElectroacupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaInstitute of Electroacupuncture and Homeostasis Regulation, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaElectroacupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaBackground: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by loss of recognition and memory. Neuroinflammation plays pivotal roles in the pathology of AD and affects the progression of the disease. Astrocyte and microglia, as main immune executors in the central nervous system (CNS), participate into the inflammatory response in AD. Glia polarize into different phenotypes during neurodegeneration. Pro-inflammatory glia produce cytokines (IL-1β, TNF-α, and IL-6) resulting into debris aggregates and neurotoxicity. Anti-inflammatory phenotypes produce cytokines (IL-4 and IL-10) to release the inflammation. Electroacupuncture is a useful treatment that has been found to slow the neurodegeneration in animals through experimentation and in humans through clinical trials. The aim of this study was to uncover the mechanisms of glia activation, microglia polarization, and cytokine secretion regulated by electroacupuncture as a treatment for AD.Methods: Twenty male Sprague–Dawley (SD) rats were randomly divided into four groups: Control group (Control), Normal saline group (NS), AD group (AD), and Electroacupuncture group (Acupuncture). The AD and Acupuncture groups were bilaterally injected with Aβ1–42 into the CA1 field of the hippocampus. The Acupuncture group received electroacupuncture stimulation on the acupoint “Baihui” (GV20) for 6 days per week for a total of 3 weeks. The Morris Water Maze (MWM) was used to evaluate learning and memory capacity. Immunofluorescence was used to stain GFAP and Iba1 of the DG and CA1 in the hippocampus, which, respectively, expressed the activation of astrocyte and microglia. The M1 microglia marker, inducible nitric oxide synthase (iNOS), and M2 marker Arginase 1 (Arg1) were used to analyze the polarization of microglia. The pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), anti-inflammatory cytokines (IL-4 and IL-10), and pathway-molecules (p65 and Stat6) were tested to analyze the glia inflammatory response by immunofluorescence and polymerase chain reaction (PCR).Results: The MWM results showed that electroacupuncture improves the escape latency time and the swimming distance of AD rats. The number of GFAP and Iba1 cells significantly increased in AD rats, but electroacupuncture decreased the cells. The iNOS-positive cells were significantly increased in AD, and electroacupuncture decreased the positive cells. Electroacupuncture elevated Arg1-positive cells in AD rats. Electroacupuncture decreased the glia pro-inflammatory cytokine expression and increased the anti-inflammatory cytokine expression in AD rats. Furthermore, electroacupuncture inhibited the NF-κB pathway molecule (p65) while raising the Stat6 pathway molecule (Stat6).Conclusion: These results provide evidence that electroacupuncture improves the recognition abilities and memory of AD rats. Electroacupuncture inhibits the activation of glia and polarizes microglia toward the M2 phenotype. Electroacupuncture decreased the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) and increased the anti-inflammatory cytokines (IL-4 and IL-10). Furthermore, electroacupuncture affects the immune responses through inhibition of NF-κB pathway but activation of Stat6 pathway.https://www.frontiersin.org/articles/10.3389/fnins.2021.689629/fullacupunctureAlzheimer’s diseasemicrogliaastrocytecytokines |
| spellingShingle | Lushuang Xie Lushuang Xie Yi Liu Ning Zhang Chenyu Li Aaron F. Sandhu Aaron F. Sandhu George Williams George Williams Yan Shen Hongying Li Qiaofeng Wu Qiaofeng Wu Shuguang Yu Shuguang Yu Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer’s Disease Frontiers in Neuroscience acupuncture Alzheimer’s disease microglia astrocyte cytokines |
| title | Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer’s Disease |
| title_full | Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer’s Disease |
| title_fullStr | Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer’s Disease |
| title_full_unstemmed | Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer’s Disease |
| title_short | Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer’s Disease |
| title_sort | electroacupuncture improves m2 microglia polarization and glia anti inflammation of hippocampus in alzheimer s disease |
| topic | acupuncture Alzheimer’s disease microglia astrocyte cytokines |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.689629/full |
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