2006 Fiscal Year Final Research Report Summary
Genetic expression alteration in autism model rats created by fetal teratogen-exposure
| Project/Area Number |
17500247
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Bunkyo University |
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Principal Investigator |
NARITA Naoko Bunkyo University, Inst. of Education, Associate Professor, 教育学部, 准教授 (40306189)
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| Co-Investigator(Kenkyū-buntansha) |
NARITA Masaaki Mie University, Graduate school of Medicine, Professor, 大学院医学系研究科, 教授 (80302404)
TASHIRO Tomoko Aoyama Gakuin University, Dept. of Science and Engineering, Professor, 理工学部, 教授 (50114541)
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| Project Period (FY) |
2005 – 2006
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| Keywords | development and differentiation / serotonin / DNA microarray |
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| Research Abstract |
Autism is a congenital neurological disorder characterized by impairment of socialization, abnormalities of communication, and limited activity and curiosity. We have recently established autism model rats by exposing embryonic day (E) 9 rat embryo to either thalidomide or valproic acid. Significant increase of hippocampal serotonin, frontal cortex dopamine, and hyperserotonemia was observed in the E9 teratogen-exposed rats when observed around postnatal day 50. In the present study, we have examined mRNA expression of various genes in the model rats and compared with control rats, to see what is the ontogene of this model rats.
First we focused on the function of serotonin transporter (5-HTT) in the autism model rat 5-HTT controls reuptake of a neurotransmitter serotonin from the extracellular space, and regulates the duration and strength of the interactions between serotonin and its receptors. We have analyzed the mRNA expression level in the E9 thalidomide exposed embryos on E11,E13, and E15. Relative mRNA expression of 5-111T gene was decreased in the thalidomide exposed embryos on E13, but increased on E15, compared to the controls. Next we performed DNA microarray of mRNA extracted from hippocampus of autism model rats and controls on P20, 30, 40 and 50, and compared over 600 neuro-related gene expression. Many changes were found including change in dopaminergic receptor expression, which is intriguing when considering increase of dopamine concentration in the hippocampus of adult autism model rats. Other genetic expression, including membrane trafficking genes, growth factors, transcription factors, were found, and future precise investigation is necessary to determine when and what genetic cascade is responsible for the characteristic social defect found in autism in humans.
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Research Products
(9 results)
