2003 Fiscal Year Final Research Report Summary
Apoptosis and neurogenesis in hippocampal injury induced by trimethyltin.
| Project/Area Number |
13670986
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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 | SHIGA UNIVERSITY OF MEDICAL SCIENCE (2003)
The University of Tokyo (2001-2002) |
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Principal Investigator |
SADAMATSU Miyuki SHIGA UNIVERSITY OF MEDICAL SICENCE, MEDICINE, LECTURER, 医学部, 講師 (90252387)
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| Co-Investigator(Kenkyū-buntansha) |
MASUI Akira SHIGA UNIVERSITY OF MEDICAL SCIENCE, MEDICINE, ASSISTANT PROFESSOR, 医学部, 助教授 (80190346)
TSUNASHIMA Koichi TOKYO UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部附属病院・精神神経科, 助教授 (30197743)
IMAI Hideki National Institute for Environmental Studies, CHIEF, 内分泌かく乱物質及びダイオキシン類の管理とリスク評価プロジェクト, 主任研究員 (00232596)
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| Project Period (FY) |
2001 – 2003
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| Keywords | HIPPOCAMPAL INJURY / TRIMETHYLTIN / NEURONAL DEATH / NEUROGENESIS |
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| Research Abstract |
The neurotoxicity of trimethyltin (TMT), an organotin compound, is well known, but the mechanism is not unclear. When TMT is administered to rats, plasma corticosterone (CORT) elevates transiently after 3-4 days later and then selective cell damages occur in CA3 and less in CA1 region. In this study, we hypothesized that the time course of apoptosis and neurogenesis in TMT-treated rats may reflect the changes in the hippocampus after HPA-axis is activated such as post-stress state. We investigated both apoptosis and neurogenesis in TMT-treated rats. Apoptotic changes reached to the peak around 5 days after TMT treatment, whereas neurogenesis appeared through 1 to 14 days after the same treatment. ADX obviously enhanced the apoptotic change, but not neurogenesis. Next, we have investigated the effects of FK506 on TMT-induced hippocampal injury in rat. Some genes with known or predicted glia-related protein are highly expressed after TMT intoxication, and down regulated after following FK506 administration, notably glutathione-S-transferase, the active oxygen scavenger and insulin-like growth factor binding protein-2 (IGFBP-2), being upregulated by astrocytic-NMDA receptors. The decreased expressions after TMT-intoxication, which increased after following FK506 administration were the expressions of the inflammation-and apoptosis-related genes, such as CaM-linase II inhibitor alpha, programmed cell death repressor BCL-X-Long and Bcl-x alpha were detected. These results suggest a neuroprotective mechanism of FK506 includes an anti-inflammatory and anti-apoptotic responses.
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