Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive-like behaviors in mice Journal Article
| Authors: | Shmelkov, S. V.; Hormigo, A.; Jing, D.; Proenca, C. C.; Bath, K. G.; Milde, T.; Shmelkov, E.; Kushner, J. S.; Baljevic, M.; Dincheva, I.; Murphy, A. J.; Valenzuela, D. M.; Gale, N. W.; Yancopoulos, G. D.; Ninan, I.; Lee, F. S.; Rafii, S. |
| Article Title: | Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive-like behaviors in mice |
| Abstract: | 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. Recently, the corticostriatal circuitry has been implicated in the pathogenesis of OCD. However, the etiology, pathophysiology and molecular basis of OCD remain unknown. Several studies indicate that the pathogenesis of OCD has a genetic component. 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. |
| Keywords: | unclassified drug; nonhuman; mouse; animals; mice; mice, knockout; animal tissue; mus; cell structure; animal experiment; animal model; nerve tissue proteins; membrane proteins; membrane protein; protein deficiency; anxiety; glutamate receptor; fluoxetine; neostriatum; synapses; behavior, animal; protein slitrk5; animal behavior; brain metabolism; neurotransmission; obsessive compulsive disorder; orbital cortex; striate cortex; compulsive behavior; grooming; obsessive-compulsive disorder; synaptic transmission |
| Journal Title: | Nature Medicine |
| Volume: | 16 |
| Issue: | 5 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2010-05-01 |
| Start Page: | 598 |
| End Page: | 602 |
| Language: | English |
| DOI: | 10.1038/nm.2125 |
| PUBMED: | 20418887 |
| PROVIDER: | scopus |
| PMCID: | PMC2907076 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 20 April 2011" - "CODEN: NAMEF" - "Source: Scopus" |
