Brain-Type Glycogen Phosphorylase Is Crucial for Astrocytic Glycogen Accumulation in Chronic Social Defeat Stress-Induced Depression in Mice
Astrocytic glycogen plays an important role in brain energy metabolism. However, the contribution of glycogen metabolism to stress-induced depression remains unclear. Chronic social defeat stress was used to induce depression-like behaviors in mice, assessed with behavioral tests. Glycogen concentra...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2021.819440/full |
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| author | Yuanyuan Zhu Ze Fan Ze Fan Qiuying Zhao Jiaqi Li Guohong Cai Rui Wang Yi Liang Naining Lu Junjun Kang Danlei Luo Huiren Tao Yan Li Jing Huang Shengxi Wu |
| author_facet | Yuanyuan Zhu Ze Fan Ze Fan Qiuying Zhao Jiaqi Li Guohong Cai Rui Wang Yi Liang Naining Lu Junjun Kang Danlei Luo Huiren Tao Yan Li Jing Huang Shengxi Wu |
| author_sort | Yuanyuan Zhu |
| collection | DOAJ |
| description | Astrocytic glycogen plays an important role in brain energy metabolism. However, the contribution of glycogen metabolism to stress-induced depression remains unclear. Chronic social defeat stress was used to induce depression-like behaviors in mice, assessed with behavioral tests. Glycogen concentration in the medial prefrontal cortex (mPFC) and the expression of key enzymes of the glycogen metabolism were investigated using Western blots, immunofluorescent staining, electron microscopy, and biochemical assays. Stereotaxic surgery and viral-mediated gene transfer were applied to knockdown or overexpress brain-type glycogen phosphorylase (PYGB) in the mPFC. The glycogen content increased in the mPFC after stress. Glycogenolytic dysfunction due to inactivation of PYGB was responsible for glycogen accumulation. Behavioral tests on astrocyte-specific PYGB overexpression mice showed that augmenting astrocytic PYGB reduces susceptibility to depression when compared with stress-susceptible mice. Conversely, PYGB genetic down-regulation in the mPFC was sufficient to induce glycogen accumulation and depression-like behaviors. Furthermore, PYGB overexpression in the mPFC decreases susceptibility to depression, at least partially by rescuing glycogen phosphorylase activity to maintain glycogen metabolism homeostasis during stress. These findings indicate that (1) glycogen accumulation occurs in mice following stress and (2) glycogenolysis reprogramming leads to glycogen accumulation in astrocytes and PYGB contributes to stress-induced depression-like behaviors. Pharmacological tools acting on glycogenolysis might constitute a promising therapy for depression. |
| first_indexed | 2024-12-20T09:51:49Z |
| format | Article |
| id | doaj.art-3d4d7beb76c84c0b897e80183e473817 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-20T09:51:49Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-3d4d7beb76c84c0b897e80183e4738172022-12-21T19:44:34ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-01-011410.3389/fnmol.2021.819440819440Brain-Type Glycogen Phosphorylase Is Crucial for Astrocytic Glycogen Accumulation in Chronic Social Defeat Stress-Induced Depression in MiceYuanyuan Zhu0Ze Fan1Ze Fan2Qiuying Zhao3Jiaqi Li4Guohong Cai5Rui Wang6Yi Liang7Naining Lu8Junjun Kang9Danlei Luo10Huiren Tao11Yan Li12Jing Huang13Shengxi Wu14Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, ChinaDepartment of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi’an, ChinaDepartment of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, ChinaDepartment of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, ChinaDepartment of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, ChinaDepartment of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, ChinaDepartment of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, ChinaDepartment of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, ChinaDepartment of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, ChinaCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Spine Surgery, Shenzhen University General Hospital, Shenzhen, ChinaCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, ChinaDepartment of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, ChinaAstrocytic glycogen plays an important role in brain energy metabolism. However, the contribution of glycogen metabolism to stress-induced depression remains unclear. Chronic social defeat stress was used to induce depression-like behaviors in mice, assessed with behavioral tests. Glycogen concentration in the medial prefrontal cortex (mPFC) and the expression of key enzymes of the glycogen metabolism were investigated using Western blots, immunofluorescent staining, electron microscopy, and biochemical assays. Stereotaxic surgery and viral-mediated gene transfer were applied to knockdown or overexpress brain-type glycogen phosphorylase (PYGB) in the mPFC. The glycogen content increased in the mPFC after stress. Glycogenolytic dysfunction due to inactivation of PYGB was responsible for glycogen accumulation. Behavioral tests on astrocyte-specific PYGB overexpression mice showed that augmenting astrocytic PYGB reduces susceptibility to depression when compared with stress-susceptible mice. Conversely, PYGB genetic down-regulation in the mPFC was sufficient to induce glycogen accumulation and depression-like behaviors. Furthermore, PYGB overexpression in the mPFC decreases susceptibility to depression, at least partially by rescuing glycogen phosphorylase activity to maintain glycogen metabolism homeostasis during stress. These findings indicate that (1) glycogen accumulation occurs in mice following stress and (2) glycogenolysis reprogramming leads to glycogen accumulation in astrocytes and PYGB contributes to stress-induced depression-like behaviors. Pharmacological tools acting on glycogenolysis might constitute a promising therapy for depression.https://www.frontiersin.org/articles/10.3389/fnmol.2021.819440/fullglycogenastrocytemedial prefrontal cortexbrain type glycogen phosphorylasedepression |
| spellingShingle | Yuanyuan Zhu Ze Fan Ze Fan Qiuying Zhao Jiaqi Li Guohong Cai Rui Wang Yi Liang Naining Lu Junjun Kang Danlei Luo Huiren Tao Yan Li Jing Huang Shengxi Wu Brain-Type Glycogen Phosphorylase Is Crucial for Astrocytic Glycogen Accumulation in Chronic Social Defeat Stress-Induced Depression in Mice Frontiers in Molecular Neuroscience glycogen astrocyte medial prefrontal cortex brain type glycogen phosphorylase depression |
| title | Brain-Type Glycogen Phosphorylase Is Crucial for Astrocytic Glycogen Accumulation in Chronic Social Defeat Stress-Induced Depression in Mice |
| title_full | Brain-Type Glycogen Phosphorylase Is Crucial for Astrocytic Glycogen Accumulation in Chronic Social Defeat Stress-Induced Depression in Mice |
| title_fullStr | Brain-Type Glycogen Phosphorylase Is Crucial for Astrocytic Glycogen Accumulation in Chronic Social Defeat Stress-Induced Depression in Mice |
| title_full_unstemmed | Brain-Type Glycogen Phosphorylase Is Crucial for Astrocytic Glycogen Accumulation in Chronic Social Defeat Stress-Induced Depression in Mice |
| title_short | Brain-Type Glycogen Phosphorylase Is Crucial for Astrocytic Glycogen Accumulation in Chronic Social Defeat Stress-Induced Depression in Mice |
| title_sort | brain type glycogen phosphorylase is crucial for astrocytic glycogen accumulation in chronic social defeat stress induced depression in mice |
| topic | glycogen astrocyte medial prefrontal cortex brain type glycogen phosphorylase depression |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2021.819440/full |
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