| Project/Area Number |
13470135
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Iwate Medical University |
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Principal Investigator |
TOHGI Hideo Iwate Medical University, Neurology, Professor, 医学部, 教授 (90155490)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGATA Munehisa Iwate Medical University, Neurology, Instructor, 医学部, 助手 (00295974)
NAGANE Yuriko Iwate Medical University, Neurology, Instructor, 医学部, 助手 (10306003)
USTUGISAWA Kimiaki Iwate Medical University, Neurology, Lecturer, 医学部, 講師 (00244913)
TAKAHASHI Satoshi Iwate Medical University, Neurology, Lecturer, 医学部, 講師 (50216719)
ABE Takasi Iwate Medical University, Neurology, Ass Professor, 医学部, 助教授 (30202667)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 2002: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | aging / α7nAChR / cDNA array / cell cycle / extracellular-signal-regulated kinase / human brain / neurite outgrowth / PC12 / α7nAChR / ERK / DNAアレイ / 老化 / ニューロン / アセチルコリン受容体 / リン酸化 |
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| Research Abstract |
Age-related changes in gene expression profile of postmortem human neocortex were investigated using cDNA array analysis. In the aging human neocortex, expression of mRNAs for neuron-specific cyclin dependent kinases (Cdks), nicotinic acetylcholine receptors (nAChRs) and molecules involved in promoting neurite outgrowth and/or neuronal plasticity decreased, and consequently increasing neuronal vulnerability might foster mRNAs expression counteractive against stresses.
PC12 cells transfected with the α7nAChR cDNA, independent of agonistic stimulation, exhibited to start the sustained expression of phospho-extracellular-signal-regulated kinases (ERKs) as immediately as expression of α7 subunit protein after transfection. PC12 cells over-expressing α7nAChR showed high migration ability, marked neurite outgrowth, adherence to the culture dish and an increase in expression of surface N-cadherin, whereas their proliferation activity was low. Examination of cell cycle distribution showed an increase in the proportion of G2-phase cells in PC 12 cells over-expressing α7nAChR. These findings suggest that, over-expression of α7nAChR induces sustained activation of ERK, which probably promotes the functions of neuron-specific Cdks and differentiation-like transformation. The cytoskeletal machinery necessary for sufficient expression of α7 nAChR may have some links to ERK and Cdk signals promoting neurite outgrowth, and their declines in the elderly may deteriorate neuronal plasticity.
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