2017 Fiscal Year Final Research Report
Validation of PSD-Zip70 knockout mice as a novel mouse model for neurodevelopmental disorder.
| Project/Area Number |
15K21319
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurophysiology / General neuroscience
Basic / Social brain science
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | PSD-Zip70 / 前頭前皮質 / シナプス / 発達障害 / 行動解析 / ノックアウトマウス / 動物モデル |
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| Outline of Final Research Achievements |
Postsynaptic protein PSD-Zip70 knockout (PSD-Zip70KO) mice possess defects in glutamate synapse transmission in the prefrontal cortex (PFC). To evaluate whether PSD-Zip70KO mice can be used as a modele for neurodevelopmental disorders such as autism spectrum disorder (ASD), we investigated their behavioral traits. As a result, PSD-Zip70KO mice did not exhibit stereotypical behavior or social ability defect, as typical ASD-like behavior. On the other hand, PSD-Zip70KO mice exhibited anxiety even without stress, and the trait was exacerbated by SD stress. Rap2 was activated and phosphorylation level of AMPA receptor GluA2 subunit at Ser880 was prominently elevated in SD-stressed mice, which leads internalization of surface-expressed AMPA receptors and decreases postsynaptic responsiveness. The PSD-Zip70-Rap2-related PFC hypofunction is involved in specifically social stress-induced anxiety. Our finding would provide valuable basis to analyze the mechanism for expression of anxiety.
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| Free Research Field |
神経科学
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