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. 2024 Oct 23;112(20):3412-3423.e6.
doi: 10.1016/j.neuron.2024.07.019. Epub 2024 Aug 19.

Astrocyte Gi-GPCR signaling corrects compulsive-like grooming and anxiety-related behaviors in Sapap3 knockout mice

Joselyn S Soto  1 , Chiranjivi Neupane  2 , Muskan Kaur  2 , Vijaya Pandey  3 , James A Wohlschlegel  3 , Baljit S Khakh  4
Affiliations

Astrocyte Gi-GPCR signaling corrects compulsive-like grooming and anxiety-related behaviors in Sapap3 knockout mice

Joselyn S Soto et al. Neuron. .

Abstract

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.

Keywords: GPCR; OCD; RNA sequencing; astrocyte; behavior; glia; proteomics; striatum.

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Conflict of interest statement

Declaration of interests UCLA filed a US provisional patent (no. 63/658,760) based on this work. B.S.K. is on the editorial advisory board of Neuron.

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