| Project/Area Number |
18K06868
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 48020:Physiology-related
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| Research Institution | Niigata University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ドパミン / モデル動物 / 覚醒記録 / 聴覚応答 / 慢性記録 / 覚醒状態 / 聴覚性応答 / ドパミン神経 / 統合失調症 / チャネル機能 / カリウムチャネル / 統合失調症モデル / 神経生理学 / サイトカイン / 脳発達 / 精神疾患 |
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| Outline of Final Research Achievements |
Epidermal growth factor (EGF) has neurotrophic effects on the developing dopaminergic neurons. Administered animals with EGF as neonate exhibit behavioral abnormalities related with schizophrenia in adulthood. As “dopamine hypothesis” is so far proposed as a hypothesis of schizophrenia, abnormal dopaminergic transmission could be related with pathophysiology. However, actual dopaminergic activity in awake state were not so far determined in this model animals, which might be related with symptoms, such as auditory hallucination. Analyses of basal activity in awake state reveal marked enhancement in the mice model. In addition, this enhancement affects auditory responses evoked by pure tone stimulation with rather higher frequency. Especially, the level of transient increase in the frequency during offset period was markedly enhanced in EGF-treated mice. Thus, these aberrant activity of dopamine neurons could be pathophysiology of this animal model.
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| Academic Significance and Societal Importance of the Research Achievements |
統合失調症は、幻覚や妄想などが伴う重篤な精神疾患であり、いまだ根治するための有効な治療法は見いだされていない。そのため疾患脳病態や発症のメカニズムの解明は、新たな治療薬開発のための治療標的の発見にもつながるものと考えられる。本研究は、疾患モデル動物のサイトカイン異常によって障害されるドパミン機能に着目して解析することで、疾患症状に関連する脳病態を明らかにしようとしたものであり、その成果は、疾患症状にかかわる神経回路機能異常やそれを引き起こす分子機序の解明につながるものと考えられる。
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