2000 Fiscal Year Final Research Report Summary
Effects of neurotrophins on the regulation of synaptic molecules and on the synaptic functions
| Project/Area Number |
11680752
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
TAKEI Nobuyuki Niigata University, Brain Research Institute, Associate Professor, 脳研究所, 助教授 (70221372)
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| Project Period (FY) |
1999 – 2000
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| Keywords | NEUROTROPHIN / BDNF / TRANSMITTER RELEASE / SYNAPTIC PLASTICITY / GLUTAMATE / PDZ PROTEINS |
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| Research Abstract |
The aim of this project is the analysis of the action of neurotrophins, especially BDNF (brain-derived neurotrophic factors), on synaptic transmission and the elucidation of its molecular basis. The effects of BDNF is classified into 2 phases (acute or chronic)by its time window and also 2 categories depending on its site of action (pre- or post-synaptic). The results of the project in each categories are as follows.
ACUTE ACTION
Pre-Synapric : BDNF induced release of excitatory amino acid neurotroansmitters, glutamate and aspartate from cerebellar granule neurons in culture (Brain Res. 1999, Neurosci. Res. 2000). The signaling cascades which leaded to the release was revealed that BDNF-TrkB activation -PLC activation-Ca2+release from intracellular store-Na+ influx-reverse transport of glutamate/glutamate release (JNR.2000)
Post-Synaptic : BDNF increased NMDA current and induced phosphorylation of NMBD receptor subunit. Both of them are mediated by Fynkinase, which activated by BDNF (presented at SFN meeting 2000).
CHRONIC ACTION
Pre-Synaptic : BDNF increased the expression of vesicular acetylcholine transporter and vesicular monoamine transporter2 in basalforebrain cholinergic and midbrain dopaminergic neurons, respectively (papers in preparation).
Post-Synaptic : BDNF increased the levels of AMPA receptor subunit proteins and enhanced AMPA current, together with the induction of the some PDZ proteins which interacted with AMPA receptor (paper in preparation).
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[Publications] Xiong, H., Yamada, K., Jourdi, H., Kawamura, M., Takei, N., Han, D., Nabeshima, T., Nawa, H.: "Regulation of nerve growth factor release by nitric oxide through cyclic GMP pathway in cortical glial cells."Mol. Pharm.. 56. 339-347 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Takei, N., Torres, E., Yuhara, A., Jongsma, H., Otto, C., Kohonen, L., Abiru, Y., Skoglosa, Y., Schutz, G., Hatanaka, H.Sofroniew, M.V, Iindholm, D.: "(2000) Pituitary adenylate cyclase activating polypeptide promotes the survival of basal forebrain cholinergic neurons in vivo and in vitro ; Comparison with effects of nerve growth factor."EUR.J.NEUROSCI.. 12. 2273-2280 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Numakawa, T., Matsumoto, T., Adachi, N., Yokomaku, D., Kojima, M., Takei, N.and Hatanaka, H.: "Brain-derived neurotrophic factor triggers a rapid glutamate release through increase of intracellular Ca2+ and Na+ in cultured cerebellar neurons."J.Neurosci. Res.. (IN PRESS). (2000)
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「研究成果報告書概要(欧文)」より
