期刊
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
卷 7, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnbeh.2013.00216
关键词
CRMP1; comprehensive behavioral test; knockout mouse; schizophrenia; mesocortical dopaminergic transmission; hyperactivity; prepulse inhibition
资金
- Ministry of Education, Science, Sports and Culture
- Japan Society for the Promotion of Science Research Fellowships for Young Scientists
- Yokohama Medical Foundation
- Grants-in-Aid for Scientific Research [25242078, 25350989, 24111546, 25116526, 12J09533, 24500444] Funding Source: KAKEN
Collapsin response mediator protein 1 (CRMP1) is one of the CRMP family members that are involved in various aspects of neuronal development such as axonal guidance and neuronal migration. Here we provide evidence that crmp1(-/-) mice exhibited behavioral abnormalities related to schizophrenia. The crmp1(-/-) mice exhibited hyperactivity and/or impaired emotional behavioral phenotype. These mice also exhibited impaired context-dependent memory and long-term memory retention. Furthermore, crmp1(-/-) mice exhibited decreased prepulse inhibition, and this phenotype was rescued by administration of chlorpromazine, a typical antipsychotic drug. In addition, in vivo microdialysis revealed that the methamphetamine-induced release of dopamine in prefrontal cortex was exaggerated in crmp1(-/-) mice, suggesting that enhanced mesocortical dopaminergic transmission contributes to their hyperactivity phenotype. These observations suggest that impairment of CRMP1 function may be involved in the pathogenesis of schizophrenia. We propose that crmp1(-/-) mouse may model endophenotypes present in this neuropsychiatric disorder.
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