2014 Fiscal Year Final Research Report
Development of gene-therapy system for psychiatric disorders by mutagenesis DREADDs
| Project/Area Number |
25660258
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Integrative animal science
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| Research Institution | Azabu University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | 前頭葉 / 扁桃体 / 不安 / DREADDs |
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| Outline of Final Research Achievements |
DREADDs is artificially expressed receptor system activated by CNO, but not endogenous ligands, and this new technology that enables to control circuit specific or molecular specific modification of neural activity. Using this technic, we challenged to ameliorate depressive/anxiety symptoms in our mouse model by assessing behavior and molecular changes. First, we developed a new AAV retro-transport vector which express CRE, and we used double infections of AAV and successfully introduced DREADDs in the PFC-amygdala circuit. When these mouse were injected with CNO, their anxiety behavior decreased (15 out of 25). In addition, FKBP5, a chaperone protein for glucocorticoid receptor, were increased in the PFC of the early-weaned mice. In addition, the expression level of FKBP5 was negatively correlated with the anxiety level, suggesting that this molecular is responsible for the higher anxiety in the early weaned mice.
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| Free Research Field |
動物行動学
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