PGD2 is implicated in neuronal development via DP1 receptor and the over-activation of PGD2-DP1 signaling during early development could be a risk factor for neurodevelopmental disorders
| Project/Area Number |
16K09967
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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 |
Pediatrics
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| Research Institution | Osaka University |
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Principal Investigator |
Mohri Ikuko 大阪大学, 連合小児発達学研究科, 准教授 (70399351)
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| Co-Investigator(Kenkyū-buntansha) |
谷池 雅子 大阪大学, 連合小児発達学研究科, 教授 (30263289)
早田 敦子 大阪大学, 連合小児発達学研究科, 助教 (70390812)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 自閉症 / PGD2 / 造血器型プロスタグランジンD合成酵素 / ミクログリア / マウス / 神経突起 / スパイン / 神経炎症 / プロスタグランジンD２ / プロスタグランジンD合成酵素 / 幼若脳 / 樹状突起 / グリア / 周産期 / プロスタグランジン / シナプス / シナプス形成 / 発現制御 / プロストグランジンD2 |
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| Outline of Final Research Achievements |
Prostaglandin D2 (PGD2) is an inflammatory mediator. During neuroinflammation, microglia produce hematopoietic PGD synthase (HPGDS). Previously, we found that HPGDS is expressed in activated microglia in the brains of Autism. In this study, we investigated whether PGD2 affects neuronal morphological development. In the primary cultured cortical neurons, PGD2 receptor agonist (DP1 agonist) increased the primary neurite number and total length of dendrites, and immature dendritic spines. In addition, repeated administration of DP1 agonist to the mouse during early postnatal period caused alterations in the dendritic morphology and the number of synapses in the prefrontal cortex. These results suggest that PGD2 is implicated in neuronal development via DP1 receptor and the over-activation of PGD2-DP1 signaling during early development could be a risk factor for autism.
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| Academic Significance and Societal Importance of the Research Achievements |
自閉症は様々な原因で発症することが知られている。近年の報告では60人に１人が自閉症であるとされ、非常に頻度が高い疾患である。近年、周産期の虚血・低酸素などのトラブルが自閉症のリスクファクターであることが報告されている。我々は本研究で周産期イベントで産生されるPGD2が神経形態に影響し、自閉症発症につながることが示された。このことより、PGD2合成酵素阻害剤等、PGD2産生抑制による自閉症発症予防法への展望がひらけ、社会的に大きな意味がある。
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Report
(5 results)
Research Products
(20 results)
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[Journal Article] Clasmatodendrosis is associated with dendritic spines and does not represent autophagic astrocyte death in influenza-associated encephalopathy.2019
Author(s)
Tachibana M, Mohri I, Hirata I, Kuwada A, Kimura-Ohba S, Kagitani-Shimono K, Fushimi H, Inoue T, Shiomi M, Kakuta Y, Takeuchi M, Murayama S, Nakayama M, Ozono K, Taniike M
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Journal Title
Brain and Development.
Volume: 41
Issue: 1
Pages: 85-95
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Atypical auditory language processing in adolescents with autism spectrum disorder.2018
Author(s)
Tanigawa J, Kagitani-Shimono K, Matsuzaki J, Ogawa R, Hanaie R, Yamamoto T, Tominaga K, Nabatame S, Mohri I, Taniike M, Ozono K.
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Journal Title
Clin Neurophysiol.
Volume: 18
Issue: 9
Pages: 31098-31098
DOI
Related Report
Peer Reviewed
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[Journal Article] Japanese Sleep Questionnaire for Elementary Schoolers (JSQ-ES): validation and population-based score distribution.2018
Author(s)
Kuwada A, Mohri I, Asano R, Matsuzawa S, Kato-Nishimura K, Hirata I, Mitsuhosi T, Kagitani-Shimono K, Nakanishi M, Tachibana M, Ohno Y, Taniike M.
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Journal Title
Sleep Medicine
Volume: 41
Pages: 69-77
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Delayed mismatch field latencies in autism spectrum disorder with abnormal auditory sensitivity: a magnetoencephalographic study.2017
Author(s)
Matsuzaki J, Kagitani-Shimono K, Sugata H, Hanaie R, Nagatani F, Yamamoto T, Tachibana M, Tominaga K, Hirata M, Mohri I, and Taniike M.
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Journal Title
Front Hum Neurosci.
Volume: 11
Pages: 446-446
DOI
Related Report
Peer Reviewed / Open Access
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