期刊
NATURE MEDICINE
卷 16, 期 5, 页码 598-U135出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2125
关键词
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资金
- US National Institutes of Health [MH079513, NS052819, HL66592, HL097797, AI080309]
- Burroughs Wellcome Foundation
- International Mental Health Research Organization
- Sackler Institute
- New York Community Trust
- Pritzker Consortium
- National Alliance for Research on Schizophrenia and Depression
- Mildred-Scheel-Stiftung, Deutsche Krebshilfe
- Gulbenkian PhD Programe in Biomedicine
- Fundacao para Ciencia e Tecnologia
- Howard Hughes Medical Institute
- Ansary Stem Cell Institute
- Anbinder and Newmans Own Foundations
- Qatar National Priorities Research Program
- Empire State Stem Cell Board
- New York State Department of Health [NYS C024180]
Obsessive-compulsive disorder (OCD) is a common psychiatric disorder defined by the presence of obsessive thoughts and repetitive compulsive actions, and it often encompasses anxiety and depressive symptoms(1,2). Recently, the corticostriatal circuitry has been implicated in the pathogenesis of OCD3,4. However, the etiology, pathophysiology and molecular basis of OCD remain unknown. Several studies indicate that the pathogenesis of OCD has a genetic component(5-8). Here we demonstrate that loss of a neuron-specific transmembrane protein, SLIT and NTRK-like protein-5 (Slitrk5), leads to OCD-like behaviors in mice, which manifests as excessive self-grooming and increased anxiety-like behaviors, and is alleviated by the selective serotonin reuptake inhibitor fluoxetine. Slitrk5(-/-) mice show selective overactivation of the orbitofrontal cortex, abnormalities in striatal anatomy and cell morphology and alterations in glutamate receptor composition, which contribute to deficient corticostriatal neurotransmission. Thus, our studies identify Slitrk5 as an essential molecule at corticostriatal synapses and provide a new mouse model of OCD-like behaviors.
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