2009 Fiscal Year Final Research Report
Research on the fundamental molecules in relation to controlling brain aging : From neuronal cytoskeleton regulation to neuronal longevity control
| Project/Area Number |
19300130
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Nagasaki University |
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Principal Investigator |
MORI Nozomu Nagasaki University, 医歯薬学総合研究科, 教授 (00130394)
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| Co-Investigator(Kenkyū-buntansha) |
SIBAZAKI Masahiko 長崎大学, 医歯薬学総合研究科, 助教 (20445109)
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| Co-Investigator(Renkei-kenkyūsha) |
KAKIZAWA Sho 長崎大学, 医歯薬学総合研究科, 講師 (40291059)
YAMAGUCHI Yoko (白石 陽子) 長崎大学, 先導生命研究センター, 研究支援推進員 (50311345)
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| Project Period (FY) |
2007 – 2009
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| Keywords | 神経可塑性 / シグナル伝達 / 神経変性 / アクチン / 微小管 |
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| Research Abstract |
While I previously established N-Shc gene deficient mouse, the so-called KO mouse, we now made N-Shc and Grit/RICS double KO mouse. In norder to understand molecular mechanisms of actin dynamics regulation via N-Shc, we examined the role of Homer/Cupidin, an anchoring molecule to actins at neuronal synapses. We also analyzed the transcriptional regulatory mechanisms of BDNF promoter by NRSF/REST. In aged brains, it has been well known that various functions, particularly in hippocampus and cerebram, do decrease, but little is known about the cerebellar function. We, therefore, asked whether synaptic LTP in cerebellum changes or not in aging, and found that it indeed declined with age. We further found that the reduction of LTP is strongly affected by oxidative stress. Since the LTP at parallel fiber-Purkinje cell synapse depend on NO (nitric oxide), we assumed and finally demonstrated that this NO-dependent LTP is impaired by oxidative stress during aging. We also analyzed the effects of HDAC6 and SIRT2 in the protein aggregate turnover in neurons, and found that HDAC6 stimulated poly glutamin-mdiated protain aggregation in neuronal cells, which may be relevant to the studies of age-related neurodegenerative diseases. Finally, we established Asian research consortium on aging.
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