Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive–like behaviors in mice
| Autor: | Till Milde, Sergey V. Shmelkov, Andrew J. Murphy, Kevin G. Bath, Muhamed Baljevic, David M. Valenzuela, Francis S. Lee, Nicholas W. Gale, Evgeny Shmelkov, Deqiang Jing, Ipe Ninan, Jared S Kushner, George D. Yancopoulos, Iva Dincheva, Adilia Hormigo, Shahin Rafii, Catia C. Proenca |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Obsessive-Compulsive Disorder
medicine.medical_specialty Serotonin reuptake inhibitor Nerve Tissue Proteins Neurotransmission Cell morphology Synaptic Transmission behavioral disciplines and activities Article General Biochemistry Genetics and Molecular Biology Pathogenesis Mice mental disorders medicine Animals Psychiatry Mice Knockout Fluoxetine Behavior Animal business.industry Glutamate receptor Membrane Proteins General Medicine Grooming Neostriatum Synapses Compulsive Behavior Anxiety Orbitofrontal cortex medicine.symptom business Neuroscience medicine.drug |
| Zdroj: | Nature Medicine. 16:598-602 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | 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 symptoms1,2. 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 component5–8. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|