Pathophysiology of schizophrenia based on analysis of the interaction between the GABAergic system and the neuroimmune system
| Project/Area Number |
17K17628
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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 |
Psychiatric science
Neurochemistry/Neuropharmacology
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| Research Institution | Gunma University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | ゲノム編集 / GABA / ノックアウトラット / 抑制姓神経伝達 / GAD67 / ミクログリア / Iba-1 / 神経新生 / 統合失調症 / 神経免疫 / グルタミン酸脱炭酸酵素 / パルブアルブミンニューロン / 神経炎症 / サイトカイン |
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| Outline of Final Research Achievements |
GAD67, one of the GABA synthetic enzymes, is downregulated in the postmortem brains of patients with schizophrenia. In the present study, GAD67 was artificially deleted in model animals (rats) using a genome editing method (GAD67KO rats). 33% of GAD67KO rats were able to develop to adulthood, and the subsequent mortality rate was not different from that of wild-type rats. Therefore, we analyzed the behavior of these rats and found phenotypes associated with schizophrenia, including cognitive impairments and altered activity levels. Histological examination revealed morphological changes of the microglia in GAD67 KO rats.
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| Academic Significance and Societal Importance of the Research Achievements |
統合失調症はその原因・病態が完全には明らかになっていない。その解明は新たな治療法の開発にも繋がると考えられ、社会的な意義も大きい。本研究では統合失調症の新たなモデル動物（GAD67KOラット）を作製することに成功した。このモデル動物はGABA神経系に注目して作られたものであるが、その他の神経システムなど（神経免疫系）にどのような影響があるかなど、ヒトでは立証困難な因果関係を解析できるツールとなることが期待できる。学術的には、精神疾患のモデル動物としてだけではなく、GABA神経系の機能を解明する上でも利用できると考えられる。
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Report
(6 results)
Research Products
(16 results)
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[Journal Article] Impact of GAD65 and/or GAD67 deficiency on perinatal development in rats.2022
Author(s)
Jiang W, Kakizaki T, Fujihara K, Miyata S, Zhang Y, Suto T, Kato D, Saito S, Shibasaki K, Ishizaki Y, Isoda K, Yokoo H, Obinata H, Hirano T, Miyasaka Y, Mashimo T, Yanagawa Y.
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Journal Title
.FASEB J .
Volume: 36(2)
Issue: 2
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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