Brain-Type Glycogen Phosphorylase Is Crucial for Astrocytic Glycogen Accumulation in Chronic Social Defeat Stress-Induced Depression in Mice.
Brain-Type Glycogen Phosphorylase Is Crucial for Astrocytic Glycogen Accumulation in Chronic Social Defeat Stress-Induced Depression in Mice.
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脑型糖原磷酸化酶对小鼠慢性社交失败应激性抑郁症星形细胞糖原积累至关重要。
DOI：
10.3389/fnmol.2021.819440
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发表时间：
2021
影响因子：
4.8
通讯作者：
Wu S
中科院分区：
文献类型：
--
作者：
Zhu Y;Fan Z;Zhao Q;Li J;Cai G;Wang R;Liang Y;Lu N;Kang J;Luo D;Tao H;Li Y;Huang J;Wu S
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.
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影响因子：
25
作者：
Menard C;Pfau ML;Hodes GE;Kana V;Wang VX;Bouchard S;Takahashi A;Flanigan ME;Aleyasin H;LeClair KB;Janssen WG;Labonté B;Parise EM;Lorsch ZS;Golden SA;Heshmati M;Tamminga C;Turecki G;Campbell M;Fayad ZA;Tang CY;Merad M;Russo SJ
通讯作者：
Russo SJ
影响因子：
3.6
作者：
Dienel, Gerald A.;Cruz, Nancy F.
通讯作者：
Cruz, Nancy F.
影响因子：
3.9
作者：
Malinska, Dominika;Testoni, Giorgia;Duszynski, Jerzy
通讯作者：
Duszynski, Jerzy
影响因子：
5.3
作者：
Duran, Jordi;Gruart, Agnes;Guinovart, Joan J.
通讯作者：
Guinovart, Joan J.
影响因子：
3.3
作者：
Bagalkot, T. R.;Jin, H. -M.;Chung, Y. -C.
通讯作者：
Chung, Y. -C.