2004 Fiscal Year Final Research Report Summary
The effects of hippocampal degeneration during development on the stress susceptibility of animal models of stress
| Project/Area Number |
15591211
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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 |
Psychiatric science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TSUNASHIMA Koichi The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (30197743)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Keiichiro The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (10323586)
KOHDA Kazuhisa Keio University, Faculty of medicine, Lecturer, 医学部, 講師 (40334388)
JINDE Seiichiro The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (30376454)
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| Project Period (FY) |
2003 – 2004
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| Keywords | hippocampus / stress / bisphenol A / estrogen receptors / Maternal separation / transthyretin / chroid plexus |
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| Research Abstract |
1.Bisphenol A (BPA) model : BPA, one of the endocrine disrupters, is widely known to act as an estrogen receptor agonist. In this study, we examined whether a perinatal exposure to a low dose BPA modulates the stress sensitivity including the functions of HPA-axis and neurotrophic factiors in later life.
In female rats, the serum corticosterone (CORT) level of BPA+ rats was significantly higher than BPA-rats under basal conditions. No difference was observed in CORT level immediately after the immobilization stress, whereas CORT level of BPA+ rats was significantly higher than BPA-rats 12 h after the immobilization stress. In male rats, there was no difference between BPA+ and BPA-rats in the serum corticosterone level under basal conditions nor after the immobilization stress. No difference was detected in the expression of GR, BDNF and c-fos mRNA between BPA+ and BPA-rats before treatment nor after a stress.
2.Maternal separation (MS) model : In experimental animals, maternal separation (MS) during neonatal period was found critical for susceptibility to stress in adult offspring. Differential gene expression caused by the MS stress was investigated with DNA microarray analysis using the rat hippocampal samples. RT-PCR was also performed to validate the results.
Expression of transthyretin (TTR) was drastically reduced in the MS group. It is known that TTR is specifically expressed in the choroid plexus (CP). When normalized by prostaglandin D synthase, TTR still indicated significant decrease. The two other CP-enriched genes, angiotensin I converting enzyme I and insulin-like growth factor II, were also significantly down-regulated in the MS group.
Considering that TTR is a carrier protein of thyroid hormone and retinol and that those factors are indispensable for neuronal development and function, significant reduction of TTR should have critical roles in generation of stress susceptibility.
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