GSK3 influences social preference and anxiety-related behaviors during social interaction in a mouse model of fragile X syndrome and autism
| Autor: | Margaret K. King, Richard S. Jope, Christopher J. Yuskaitis, Marjelo A. Mines, Eléonore Beurel |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Neurological Disorders/Developmental and Pediatric Neurology lcsh:Medicine Anxiety Choice Behavior Fragile X Mental Retardation Protein Glycogen Synthase Kinase 3 Mice 0302 clinical medicine lcsh:Science Mice Knockout 0303 health sciences Multidisciplinary Behavior Animal Neuroscience/Neurodevelopment Fragile X syndrome Mental Health Neurological Disorders/Neuropharmacology Knockout mouse Mental Health/Psychopharmacology Research Article congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty animal structures macromolecular substances Stimulus (physiology) Biology Lithium Neurological Disorders 03 medical and health sciences medicine Animals Mental Health/Developmental and Pediatric Neurology Autistic Disorder Psychiatry Social Behavior GSK3B 030304 developmental biology Glycogen Synthase Kinase 3 beta lcsh:R medicine.disease FMR1 Social relation Disease Models Animal Fragile X Syndrome Autism lcsh:Q Neuroscience 030217 neurology & neurosurgery Social behavior |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 3, p e9706 (2010) |
| ISSN: | 1932-6203 |
| Popis: | Background Nearly 1% of children in the United States exhibit autism spectrum disorders, but causes and treatments remain to be identified. Mice with deletion of the fragile X mental retardation 1 (Fmr1) gene are used to model autism because loss of Fmr1 gene function causes Fragile X Syndrome (FXS) and many people with FXS exhibit autistic-like behaviors. Glycogen synthase kinase-3 (GSK3) is hyperactive in brains of Fmr1 knockout mice, and inhibition of GSK3 by lithium administration ameliorates some behavioral impairment in these mice. We extended our studies of this association by testing whether GSK3 contributes to socialization behaviors. This used two mouse models with disrupted regulation of GSK3, Fmr1 knockout mice and GSK3 knockin mice, in which inhibitory serines of the two isoforms of GSK3, GSK3alpha and GSK3beta, are mutated to alanines, leaving GSK3 fully active. Methodology/principal findings To assess sociability, test mice were introduced to a restrained stimulus mouse (S1) for 10 min, followed by introduction of a second restrained stimulus mouse (S2) for 10 min, which assesses social preference. Fmr1 knockout and GSK3 knockin mice displayed no deficit in sociability with the S1 mouse, but unlike wild-type mice neither demonstrated social preference for the novel S2 mouse. Fmr1 knockout mice displayed more anxiety-related behaviors during social interaction (grooming, rearing, and digging) than wild-type mice, which was ameliorated by inhibition of GSK3 with chronic lithium treatment. Conclusions/significance These results indicate that impaired inhibitory regulation of GSK3 in Fmr1 knockout mice may contribute to some socialization deficits and that lithium treatment can ameliorate certain socialization impairments. As discussed in the present work, these results suggest a role for GSK3 in social behaviors and implicate inhibition of GSK3 as a potential therapeutic. |
| Databáze: | OpenAIRE |
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