| Project/Area Number |
18591142
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Mie University |
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Principal Investigator |
NARITA Masaaki Mie University, GRADUATE SCHOOL OF MEDICINE, PROFESSOR (80302404)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAMOTO Shinya UNIVERSITY OF TSUKUBA, GRADUATE SCHOOL OF COMPREHENSIVE HUMAN SCIENCES, 教授 (60251005)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | autism / model animal / バイオマーカー / BDNF / セロトニン |
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| Research Abstract |
Autism is thought to occur from early embryonic stage. Biomarkers for diagnosis of autism is necessary. In the field of autism basic research, chemicals including thalidomide(THAL) and valproic acid(VPA) are known to induce autism when taken at early gestational stage in human. We have previously established autism model rats by exposing THAL or VPA to embryonic(E) day 9 rats(Pediatr Res, 52 ; 576 : 2002, Int J Dev Neurosci, 23 ; 287 : 2005). Migration disorder of serotonergic(5-HT) neurons was observed in the adult.
Previously, we have found that brain-derived neurotrophic factor(BDNF) and neurotrophins-4(NT-4) are useful for the diagnostic biomarkers for autism. In this research, we found that BDNF and NT-4 are also useful for the subtype classification of autism in clinics. Also, dramatic delay of serotonergic development was observed in the embryos of autism model rats. Expression of sonic hedgehog(shh) were perturbed in the embryos of autism rats using whole mount in situ hybridization and real time PCR technique.
These results indicate that two potential autism-inducing teratogens, THAL and VPA, may disrupt early 5-HT neuronal development in the embryos through the perturbation of shh signal pathway, and thus may cause irreversible changes observed in the adult.
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