| Project/Area Number |
11694284
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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 | KAGAWA MEDICAL UNIVERSITY |
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Principal Investigator |
TOKUDA Masaaki Kagawa Medical University, Physiology, Professor, 医学部, 教授 (10163974)
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| Co-Investigator(Kenkyū-buntansha) |
OKABE Akinobu Kagawa Medical University, Microbiology, Professor, 医学部, 教授 (20093677)
SUGIMOTO Katsuyoshi Kagawa Medical University, Physiology, Research Associate, 医学部, 助手 (80322270)
KOBAYASHI Ryoji Kagawa Medical University, Chemistry, Professor, 医学部, 教授 (00020917)
TAKEUCHI Yoshiki Kagawa Medical University, Chemistry, Professor, 医学部, 教授 (20116619)
山口 文徳 香川医科大学, 医学部, 助手 (40271085)
松下 治 香川医科大学, 医学部, 助教授 (00209537)
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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 |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | calbrain / CaM kinase II / LTP / S100 / brain / hypothermia / NMDA / alcoholism / カルシウム結合蛋白質 / 記憶 / Ca^<2+> / calmodulin-dependent protein kinase II / calcineurin / NMR |
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| Research Abstract |
A novel Ca2+-binding protein, termed calbrain, was isolated from a human brain cDNA library. The analysis of deduced amino acid sequence revealed that calbrain contains two putative EF-hand motifs that show significantly high homology to those of the calmodulin(CaM)family rather than two EF-hand protein families. Studies in vitro revealed that calbrain competitively inhibited CaM binding to Ca2+/calmodulin-dependent kinase II(Ki = 129 nM)and reduced its kinase activily and autophosphorylation.
Ca2+/calmodulin-dependent protein kinase I(CaM-kinase I)in rat retina was shown to be present in rat retina. Developmental studies revealed that CaM-kinase I expression increased in accordance with postnatal development. Expression of CaM-kinase I in the retinas of rats raised in the complete darkness markedly decreased.
CaMK-I was shown to mainly localize in the cytoplasm of the control and LTP-induced neurons, and a significant increase of immunoreactivity was observed in the latter neurons. A part of CaMK-I was found to translocate to the nuclei of LTP-induced hippocampal CA1 neurons.
To investigate the mechanism of chronic cell death following postischemic hypothermia, the change of N-methyl-D-aspartate receptor(NMDAR)was examined in the CA1 subfield of the gerbil hippocampus. At 1 week following postischemic hypothermia(32 degrees Cx4 h), all CA1 neurons survived ; however, immunoreactivity of NMDAR1 increased in neuronal perikarya whereas decreased in dendrites in the CA1 neurons. LTP was also significantly depressed at 1 week after hypothermia.
Morphological changes of the suprachiasmatic nucleus(SCN)of the hypothalamus were investigated in mice exhibiting intoxication signs of stages 2 or 3 after a short application term of 6% ethanol. Alterations in glial cells and neurons were examined using anti-glial fibrillary acidic protein(GFAP)and short-term ethanol exposure led to strong expression of GFAP-immunoreactivily(GFAP-IR)in the dorsomedial part of the SCN.
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