2018 Fiscal Year Final Research Report
Association between brain malformations of neurodevelopmental psychiatric disorders and PGE2-EP1 signaling
| Project/Area Number |
16K08421
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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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| Research Field |
Medical pharmacy
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| Research Institution | Meijo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吉見 陽 名城大学, 薬学部, 助教 (00637671)
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| Research Collaborator |
OZAKI Norio
MOURI Akihiro
HIDA Hirotake
UCHIDA Mizuki
MUTO Rina
TAKASU Mitsuhira
KITAGAKI Shinji
HIRAMATSU Masayuki
MAMIYA Takayoshi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 統合失調症 / 神経発達障害仮説 / プロスタグランジンE2 / フェンシクリジン / リンパ芽球様細胞株 / 行動解析 / 遺伝子発現解析 |
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| Outline of Final Research Achievements |
To elucidate the pathogenesis of psychiatric disorders based on the neurodevelopmental hypothesis, we examined psychiatric functions in psychiatric disorder-like model mice exposed to environmental factors, which related to the onset of psychiatric disorders and pathological conditions. In mice neonatally injected prostaglandin E2 as a susceptibility factor for psychobehavioral abnormalities, emotional and cognitive dysfunctions were observed at postnatal day (PD)70, but not PD35. Mice at PD35 showed a decrease in hyperpotassium-induced glutamate release in the prefrontal cortex. In the prefrontal cortex and hippocampus of mice at PD35 or PD70, the changes in gene expression related to regulation of cytoskeleton, dendrite development, behavioral fear response, etc. were observed. It was revealed that the exposure of susceptibility factors related to bio-psycho-social conditions in early stage of neurodevelopment caused neurofunctional and psychobehavioral abnormalities.
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| Free Research Field |
神経精神薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
患者由来末梢サンプル（LCL）において、中枢神経機能と関連のある遺伝子の発現変化が認められ、疾患モデルであるPCP投与マウスの末梢および中枢サンプル（血液とPFC）において、共通して発現変化を示す遺伝子が同定された。したがって、精神疾患の中枢における分子病態像が末梢に反映されている可能性があり、発症や治療反応性の予測に有用な生物学的指標となりうる。加えて、ストレスなどの外来環境因子の曝露により生じるエピジェネティック制御機構を明らかにすることで、精神疾患の発症脆弱性の形成や発症のメカニズム解明の一助になると考える。
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