GluN2A/ERK/CREB Signaling Pathway Involved in Electroacupuncture Regulating Hypothalamic-Pituitary-Adrenal Axis Hyperactivity
The hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis caused by stress will inevitably disrupt the homeostasis of the neuroendocrine system and damage physiological functions. It has been demonstrated that electroacupuncture (EA) can modulate HPA axis hyperactivity during the perioperat...
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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.2021.703044/full |
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| author | Yu Wang Jing Han Jing Zhu Mizhen Zhang Minda Ju Yueshan Du Zhanzhuang Tian |
| author_facet | Yu Wang Jing Han Jing Zhu Mizhen Zhang Minda Ju Yueshan Du Zhanzhuang Tian |
| author_sort | Yu Wang |
| collection | DOAJ |
| description | The hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis caused by stress will inevitably disrupt the homeostasis of the neuroendocrine system and damage physiological functions. It has been demonstrated that electroacupuncture (EA) can modulate HPA axis hyperactivity during the perioperative period. As the initiating factor of the HPA axis, hypothalamic corticotrophin-releasing hormone (CRH) is the critical molecule affected by EA. However, the mechanism by which EA reduces CRH synthesis and secretion remains unclear. Activated N-methyl-D-aspartate receptor (NMDAR) has been linked to over-secretion of hypothalamic CRH induced by stress. To determine whether NMDAR is involved in EA regulating the over-expression of CRH, a surgical model of partial hepatectomy (HT) was established in our experiment. The effect of EA on hypothalamic NMDAR expression in HT mice was examined. Then, we investigated whether the extracellular regulated protein kinases (ERK)/cyclic adenosine monophosphate response element-binding protein (CREB) signaling pathway mediated by NMDAR was involved in EA regulating HPA axis hyperactivity. It was found that surgery enhanced the expression of hypothalamic CRH and caused HPA axis hyperactivity. Intriguingly, EA effectively suppressed the expression of CRH and decreased the activation of GluN2A (NMDAR subunit), ERK, and CREB in HT mice. GluN2A, ERK, and CREB antagonists had similar effects on normalizing the expression of CRH and HPA axis function compared with EA. Our findings suggested that surgery enhanced the activation of the hypothalamic GluN2A/ERK/CREB signaling pathway, thus promoting the synthesis and secretion of CRH. EA suppressed the phosphorylation of GluN2A, ERK, and CREB in mice that had undergone surgery, indicating that the GluN2A/ERK/CREB signaling pathway was involved in EA alleviating HPA axis hyperactivity. |
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| last_indexed | 2024-12-14T19:05:30Z |
| publishDate | 2021-09-01 |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-a23f0bed377d4606becd037fcbcffdc02022-12-21T22:50:52ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-09-011510.3389/fnins.2021.703044703044GluN2A/ERK/CREB Signaling Pathway Involved in Electroacupuncture Regulating Hypothalamic-Pituitary-Adrenal Axis HyperactivityYu Wang0Jing Han1Jing Zhu2Mizhen Zhang3Minda Ju4Yueshan Du5Zhanzhuang Tian6State Key Laboratory of Medical Neurobiology, Department of Integrative Medicine and Neurobiology, Brain Science Collaborative Innovation Center, School of Basic Medical Sciences, Institutes of Brain Science, Fudan Institutes of Integrative Medicine, Fudan University, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, Department of Integrative Medicine and Neurobiology, Brain Science Collaborative Innovation Center, School of Basic Medical Sciences, Institutes of Brain Science, Fudan Institutes of Integrative Medicine, Fudan University, Shanghai, ChinaDepartment of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, Department of Integrative Medicine and Neurobiology, Brain Science Collaborative Innovation Center, School of Basic Medical Sciences, Institutes of Brain Science, Fudan Institutes of Integrative Medicine, Fudan University, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, Department of Integrative Medicine and Neurobiology, Brain Science Collaborative Innovation Center, School of Basic Medical Sciences, Institutes of Brain Science, Fudan Institutes of Integrative Medicine, Fudan University, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, Department of Integrative Medicine and Neurobiology, Brain Science Collaborative Innovation Center, School of Basic Medical Sciences, Institutes of Brain Science, Fudan Institutes of Integrative Medicine, Fudan University, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, Department of Integrative Medicine and Neurobiology, Brain Science Collaborative Innovation Center, School of Basic Medical Sciences, Institutes of Brain Science, Fudan Institutes of Integrative Medicine, Fudan University, Shanghai, ChinaThe hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis caused by stress will inevitably disrupt the homeostasis of the neuroendocrine system and damage physiological functions. It has been demonstrated that electroacupuncture (EA) can modulate HPA axis hyperactivity during the perioperative period. As the initiating factor of the HPA axis, hypothalamic corticotrophin-releasing hormone (CRH) is the critical molecule affected by EA. However, the mechanism by which EA reduces CRH synthesis and secretion remains unclear. Activated N-methyl-D-aspartate receptor (NMDAR) has been linked to over-secretion of hypothalamic CRH induced by stress. To determine whether NMDAR is involved in EA regulating the over-expression of CRH, a surgical model of partial hepatectomy (HT) was established in our experiment. The effect of EA on hypothalamic NMDAR expression in HT mice was examined. Then, we investigated whether the extracellular regulated protein kinases (ERK)/cyclic adenosine monophosphate response element-binding protein (CREB) signaling pathway mediated by NMDAR was involved in EA regulating HPA axis hyperactivity. It was found that surgery enhanced the expression of hypothalamic CRH and caused HPA axis hyperactivity. Intriguingly, EA effectively suppressed the expression of CRH and decreased the activation of GluN2A (NMDAR subunit), ERK, and CREB in HT mice. GluN2A, ERK, and CREB antagonists had similar effects on normalizing the expression of CRH and HPA axis function compared with EA. Our findings suggested that surgery enhanced the activation of the hypothalamic GluN2A/ERK/CREB signaling pathway, thus promoting the synthesis and secretion of CRH. EA suppressed the phosphorylation of GluN2A, ERK, and CREB in mice that had undergone surgery, indicating that the GluN2A/ERK/CREB signaling pathway was involved in EA alleviating HPA axis hyperactivity.https://www.frontiersin.org/articles/10.3389/fnins.2021.703044/fullGluN2A/ERK/CREB signaling pathwayHPA axiselectroacupunctureCRHsurgical trauma |
| spellingShingle | Yu Wang Jing Han Jing Zhu Mizhen Zhang Minda Ju Yueshan Du Zhanzhuang Tian GluN2A/ERK/CREB Signaling Pathway Involved in Electroacupuncture Regulating Hypothalamic-Pituitary-Adrenal Axis Hyperactivity Frontiers in Neuroscience GluN2A/ERK/CREB signaling pathway HPA axis electroacupuncture CRH surgical trauma |
| title | GluN2A/ERK/CREB Signaling Pathway Involved in Electroacupuncture Regulating Hypothalamic-Pituitary-Adrenal Axis Hyperactivity |
| title_full | GluN2A/ERK/CREB Signaling Pathway Involved in Electroacupuncture Regulating Hypothalamic-Pituitary-Adrenal Axis Hyperactivity |
| title_fullStr | GluN2A/ERK/CREB Signaling Pathway Involved in Electroacupuncture Regulating Hypothalamic-Pituitary-Adrenal Axis Hyperactivity |
| title_full_unstemmed | GluN2A/ERK/CREB Signaling Pathway Involved in Electroacupuncture Regulating Hypothalamic-Pituitary-Adrenal Axis Hyperactivity |
| title_short | GluN2A/ERK/CREB Signaling Pathway Involved in Electroacupuncture Regulating Hypothalamic-Pituitary-Adrenal Axis Hyperactivity |
| title_sort | glun2a erk creb signaling pathway involved in electroacupuncture regulating hypothalamic pituitary adrenal axis hyperactivity |
| topic | GluN2A/ERK/CREB signaling pathway HPA axis electroacupuncture CRH surgical trauma |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.703044/full |
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