Department of Neurobiology and Department of General Intensive Care Unit of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310058, China.
NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310058, China; Department of Neurobiology and Department of Ophthalmology of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
Neurosci Lett. 2022 Jul 27;784:136766. doi: 10.1016/j.neulet.2022.136766. Epub 2022 Jun 30.
Major depressive disorder (MDD) is one of the most common and disabling mental disorders that characterized by profound disturbances in emotional regulation, motivation, cognition, and the physiology of affected individuals. Although MDD was initially thought to be primarily triggered through neuronal dysfunction, the pathological alterations in astrocytic function have been previously reported in MDD. We report that chronic restraint stress (CRS) induces astrocyte activation and decreases expression of astrocytic mGluR5 in the hippocampal CA1 of susceptible mice exhibited depressive-like behaviors. Reducing expression of astrocytic mGluR5 in dorsal CA1 simulates CRS-induced depressive-like behaviors and impairs excitatory synaptic function in mice, while overexpression of astrocytic mGluR5 in dorsal CA1 rescues CRS-induced depressive-like traits and excitatory synaptic dysfunction. Thus, we provide direct evidence for an important role of astrocytic mGluR5 in producing the behavioral phenotypes of MDD, supporting astrocytic mGluR5 may serve as an effective therapeutic target for MDD.
重度抑郁症（MDD）是最常见和致残的精神障碍之一，其特征是情绪调节、动机、认知和受影响个体的生理学出现深刻障碍。尽管最初认为 MDD 主要是由神经元功能障碍引发的，但以前已经报道过 MDD 中星形胶质细胞功能的病理性改变。我们报告说，慢性束缚应激（CRS）诱导易感小鼠海马 CA1 中的星形胶质细胞激活，并降低星形胶质细胞 mGluR5 的表达，表现出类似抑郁的行为。减少背侧 CA1 中星形胶质细胞 mGluR5 的表达模拟 CRS 诱导的类似抑郁的行为，并损害小鼠的兴奋性突触功能，而在背侧 CA1 中过度表达星形胶质细胞 mGluR5 则可挽救 CRS 诱导的类似抑郁的特征和兴奋性突触功能障碍。因此，我们提供了星形胶质细胞 mGluR5 在产生 MDD 行为表型方面的重要作用的直接证据，支持星形胶质细胞 mGluR5 可能成为 MDD 的有效治疗靶点。
