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 |
Section | 一般 |
Research Field |
Medical pharmacy
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Research Institution | Meijo University |
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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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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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 / 神経発達障害 / 精神疾患 / モデル動物 / リスク因子 / プロスタグランジン / 層構造形成 / 神経-グリア細胞 |
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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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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Report
(4 results)
Research Products
(75 results)
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[Journal Article] Juvenile social defeat stress exposure persistently impairs social behaviors and neurogenesis.2018
Author(s)
Mouri A, Ukai M, Uchida M, Hasegawa S, Taniguchi M, Ito T, Hida H, Yoshimi A, Yamada K, Kunimoto S, Ozaki N, Nabeshima T, Noda Y.
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Journal Title
Neuropharmacology.
Volume: 133
Pages: 23-37
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The involvement of brain-derived neurotrophic factor in 3,4-methylenedioxymethamphetamine-induced place preference and behavioral sensitization2017
Author(s)
Akihiro Mouri, Yukihiro Noda, Minae Niwa, Yurie Matsumoto, Takayoshi Mamiya, Atsumi Nitta, Kiyofumi Yamada, Shoei Furukawa, Tatsunori Iwamura, Toshitaka Nabeshima
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Journal Title
Behavioural Brain Research
Volume: 329
Pages: 157-165
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] High-resolution copy number variation analysis of schizophrenia in Japan.2017
Author(s)
Kushima I, Aleksic B, Nakatochi M, Shimamura T, Shiino T, Yoshimi A, Kimura H, Takasaki Y, Wang C, Xing J, Ishizuka K, Oya-Ito T, Nakamura Y, Arioka Y, Maeda T, Yamamoto M, Yoshida M, Noma H, Hamada S, Morikawa M, Uno Y, Okada T, Iidaka T, Iritani S, Yamamoto T,
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Journal Title
Molecular Psychiatry
Volume: 22
Issue: 3
Pages: 430-440
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] An analysis of behavioral and genetic risk factors for chemotherapy- induced nausea and vomiting in Japanese subjects2016
Author(s)
Naoki Mukoyama, Akira Yoshimi, Aya Goto, Haruka Kotani, Kazuhiro Ishikawa, Noriko Miyazaki, Masayuki Miyazaki, Kiyofumi Yamada, Fumitaka Kikkawa, Yoshinori Hasegawa, Norio Ozaki, Yukihiro Noda
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Journal Title
Biol. Pharm. Bull.
Volume: 39
Pages: 1852-1858
NAID
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Resequencing and Association Analysis of Six PSD-95-Related Genes as Possible Susceptibility Genes for Schizophrenia and Autism Spectrum Disorders2016
Author(s)
Xing J, Kimura H, Wang C, Ishizuka K, Kushima I, Arioka Y, Yoshimi A, Nakamura Y, Shiino T, Oya-Ito T, Takasaki Y, Uno Y, Okada T, Iidaka T, Aleksic B, Mori D, Ozaki N.
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
Pages: 27491-27491
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Mutation screening of GRIN2B in schizophrenia and autism spectrum disorder in a Japanese population.2016
Author(s)
Takasaki Y, Koide T, Wang C, Kimura H, Xing J, Kushima I, Ishizuka K, Mori D, Sekiguchi M, Ikeda M, Aizawa M, Tsurumaru N, Iwayama Y, Yoshimi A, Arioka Y, Yoshida M, Noma H, Oya-Ito T, Nakamura Y, Kunimoto S, Aleksic B, Uno Y, Okada T, Ujike H, Egawa J, Kuwabara H, Someya T, Yoshikawa T, Iwata N, Ozaki N
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
Pages: 33311-33311
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Involvement of glutamate receptors in the impairment of social behaviors induced by social defeat stress exposure as juveniles2018
Author(s)
Mikio Yoshida, Sho Hasegawa, Akira Yoshimi, Akihiro Mouri, Yoji Uchida, Hirotake Hida, Masayoshi Mishina, Kiyofumi Yamada, Norio Ozaki, Toshitaka Nabeshima, Yukihiro Noda
Organizer
第92回日本薬理学会年会
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