Work

Faculty Opinions recommendation of Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice.

Year: 2007

Type: peer-review

Abstract: Obsessive-compulsive disorder (OCD) is an anxiety-spectrum disorder characterized by persistent intrusive thoughts (obsessions) and repetitive actions (compulsions).Dysfunction of cortico-striatothalamo-cortical circuitry is implicated in OCD, though the underlying pathogenic mechanisms are unknown.SAP90/PSD95-associated protein 3 (SAPAP3) is a postsynaptic scaffolding protein at excitatory synapses that is highly expressed in the striatum.Here we show that mice with genetic deletion of SAPAP3 exhibit increased anxiety and compulsive grooming behavior leading to facial hair loss and skin lesions; both behaviors are alleviated by a selective serotonin reuptake inhibitor.Electrophysiological, structural, and biochemical studies of SAPAP3 mutant mice reveal defects in cortico-striatal synapses.Furthermore, lentiviral-mediated selective expression of SAPAP3 in the striatum rescues the synaptic and behavioral defects of SAPAP3 mutant mice.These findings demonstrate a critical role for SAPAP3 at cortico-striatal synapses and emphasize the importance of cortico-striatal circuitry in OCD-like behaviors.

Source: Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

DOI: 10.3410/f.1090653.545891

Author: Daniel Geschwind

Institution: University of California, Los Angeles

Language: English

Topic: Obsessive-Compulsive Spectrum Disorders

Subfield: Clinical Psychology

Field: Psychology

Domain: Social Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Science Foundation, McKnight Foundation, National Alliance for Research on Schizophrenia and Depression, National Institutes of Health, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences

OpenAlex ID: W4206273883

Cites: 42

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Related to: 10