Publications

Haya H Al Muhannadi
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Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive-like behaviors in mice

Author(s): Shmelkov, SV (Shmelkov, Sergey V.); Hormigo, A (Hormigo, Adilia); Jing, DQ (Jing, Deqiang); Proenca, CC (Proenca, Catia C.); Bath, KG (Bath, Kevin G.); Milde, T (Milde, Till); Shmelkov, E (Shmelkov, Evgeny); Kushner, JS (Kushner, Jared S.); Baljevic, M (Baljevic, Muhamed); Dincheva, I (Dincheva, Iva); Murphy, AJ (Murphy, Andrew J.); Valenzuela, DM (Valenzuela, David M.); Gale, NW (Gale, Nicholas W.); Yancopoulos, GD (Yancopoulos, George D.); Ninan, I (Ninan, Ipe); Lee, FS (Lee, Francis S.); Rafii, S (Rafii, Shahin)

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.

Author(s):  Shmelkov, SV (Shmelkov, Sergey V.); Hormigo, A (Hormigo, Adilia); Jing, DQ (Jing, Deqiang); Proenca, CC (Proenca, Catia C.); Bath, KG (Bath, Kevin G.); Milde, T (Milde, Till); Shmelkov, E (Shmelkov, Evgeny); Kushner, JS (Kushner, Jared S.); Baljevic, M (Baljevic, Muhamed); Dincheva, I (Dincheva, Iva); Murphy, AJ (Murphy, Andrew J.); Valenzuela, DM (Valenzuela, David M.); Gale, NW (Gale, Nicholas W.); Yancopoulos, GD (Yancopoulos, George D.); Ninan, I (Ninan, Ipe); Lee, FS (Lee, Francis S.); Rafii, S (Rafii, Shahin)
Source:  NATURE MEDICINE, 16 (5): 598-U135 MAY 2010
Language:  English
Document Type:  Article
KeyWords Plus:  CAUDATE-NUCLEUS; SHORT-TERM; LONG-TERM; DISORDER; FAMILY; MODELS; BRAIN; EPIDEMIOLOGY; PLASTICITY; VARIANTS
Addresses:  [Jing, Deqiang; Proenca, Catia C.; Bath, Kevin G.; Dincheva, Iva; Lee, Francis S.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA; [Shmelkov, Sergey V.; Hormigo, Adilia; Milde, Till; Shmelkov, Evgeny; Kushner, Jared S.; Baljevic, Muhamed; Rafii, Shahin] Weill Cornell Med Coll, Howard Hughes Med Inst, Ansary Stem Cell Inst, New York, NY USA; [Shmelkov, Sergey V.; Hormigo, Adilia; Milde, Till; Shmelkov, Evgeny; Kushner, Jared S.; Baljevic, Muhamed; Rafii, Shahin] Weill Cornell Med Coll, Dept Geriatr Med, New York, NY USA; [Hormigo, Adilia] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA; [Hormigo, Adilia] Weill Cornell Med Coll, Dept Neurol, New York, NY USA; [Proenca, Catia C.] Inst Gulbenkian Ciencias, Gulbenkian PhD Programe Biomed, Oeiras, Portugal; [Dincheva, Iva; Lee, Francis S.] Weill Cornell Med Coll, Dept Pharmacol, New York, NY USA; [Murphy, Andrew J.; Valenzuela, David M.; Gale, Nicholas W.; Yancopoulos, George D.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA; [Ninan, Ipe] NYU, Dept Psychiat, Langone Med Ctr, New York, NY 10016 USA
Reprint Address:  Lee, FS, Weill Cornell Med Coll, Dept Psychiat, New York, NY USA.
Funding Agency:  US National Institutes of Health - 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
Publisher:  NATURE PUBLISHING GROUP
Publisher Address:  75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
ISSN:  1078-8956
29-char Source Abbrev.:  NATURE MED
ISO Source Abbrev.:  Nat. Med.
Subject Category:  Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental
ISI Document Delivery No.:  592QP
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