| Project/Area Number |
11670104
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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 |
General pharmacology
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| Research Institution | TOKYO UNIVERSITY OF PHARMACY & LIFE SCIENCE |
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Principal Investigator |
TAKEO Satosi TOKYO UNIVERSITY OF PHARMACY & LIFE SCIENCE, FACULTY OF PHARMACEUTICAL SCIENCES, PROFESSOR, 薬学部, 教授 (00136722)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAGI Norio TOKYO UNIVERSITY OF PHARMACY & LIFE SCIENCE, FACULTY OF PHARMACEUTICAL SCIENCES, ASSISTANT PROFESSOR, 薬学部, 助手 (50318193)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | REGENERATION OF THE NEURONAL NETWORK / NERVE GROWTH FACTOR / BDNF / GAP-43 / CELL ADHESION MOLECULE / CEREBROVASCULAR DEMENTIA / ACETYLCHOLINE / TYROSINE PHOSPHORYLATION OF G PROTEIN / 脳血管性痴呆症 / マイクロスフェア塞栓 / シナプトフィジン / MAP-2 / コリンアセチルトランスフェラーゼ |
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| Research Abstract |
We investigated changes in signal transduction pathways via muscarinic acetylcholine receptor (mAChR) in hippocampal slices after microsphere embolism (ME) in this term of research project. Our findings demonstrated that stimulation of mAChR fails to activate MAP kinase in the ipsilateral, but not in the contralateral hippocampus of ischemic rats. The stimulation of mAChR with carbachol induced tyrosine phosphorylation of the Gα_<q/11> subunit in the contralateral, but not in the ipsilateral hippocampus. These results suggest that failure in mAChR-induced tyrosine phosphorylation of the Gα_<q/11> subunit in the ischemic hippocampus may be involved in alterations of ERK signal transduction.
We further examined alterations in factors involved in the regeneration of the neuronal network in the hippocampus of rats with ME.The immunohistochemical study showed increases in GAP-43, a marker of axonal sprouting ; synaptophysin, a inarker of presynaptic nerve ; and BDNF, a neurotrophic factor and a decrease in the amount of L1, an adhesion molecule in some areas of the hippocampal ischemic penumbra of such animals. These results suggest that some, but not all, factors for regeneration of the neuronal network in the ischemic penumbra respond to sustained cerebral ischemia for a certain period. Immunochemical analysis, however, showed decreases in the absolute amounts of GAP-43 and L1 proteins in the ipsilateral hippocampus of the ME animal. The lack of an increase in L1 in the ischemic penumbra of the hippocampus of the ME animal suggests that production of cell adhesion molecules in response to cerebral ischemia may play a role in the regeneration of the neuronal network of the central nervous system after ischemic brain injury.
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