Astrocytes are morphologically complex cells that serve essential roles. They are widely implicated in central nervous system (CNS) disorders, with changes in astrocyte morphology and gene expression accompanying disease. In the Sapap3 knockout (KO) mouse model of compulsive and anxiety-related behaviors related to obsessive-compulsive disorder (OCD), striatal astrocytes display reduced morphology and altered actin cytoskeleton and Gi-G-protein-coupled receptor (Gi-GPCR) signaling proteins. Here, we show that normalizing striatal astrocyte morphology, actin cytoskeleton, and essential homeostatic support functions by targeting the astrocyte Gi-GPCR pathway using chemogenetics corrected phenotypes in Sapap3 KO mice, including anxiety-related and compulsive behaviors. Our data portend an astrocytic pharmacological strategy for rescuing phenotypes in brain disorders that include compromised astrocyte morphology and tissue support.

中文翻译：

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星形胶质细胞 Gi-GPCR 信号传导可纠正 Sapap3 敲除小鼠的强迫性样梳理和焦虑相关行为


星形胶质细胞是形态复杂的细胞，起着重要作用。它们与中枢神经系统 （CNS） 疾病广泛相关，伴随疾病的星形胶质细胞形态和基因表达发生变化。在与强迫症 （OCD） 相关的强迫和焦虑相关行为的 Sapap3 敲除 （KO） 小鼠模型中，纹状体星形胶质细胞表现出形态降低和肌动蛋白细胞骨架和 Gi-G 蛋白偶联受体 （Gi-GPCR） 信号蛋白的改变。在这里，我们表明，通过使用化学遗传学靶向星形胶质细胞 Gi-GPCR 通路来正常化纹状体星形胶质细胞形态、肌动蛋白细胞骨架和必要的稳态支持功能，从而纠正了 Sapap3 KO 小鼠的表型，包括焦虑相关和强迫行为。我们的数据预示着一种星形胶质细胞药理学策略，用于挽救脑部疾病中的表型，包括受损的星形胶质细胞形态和组织支持。