1993 Fiscal Year Final Research Report Summary
A study on the cell death of primary cultured rat's cortical neurons induced by exicitatory amino acids and protective strategies against it.
Project/Area Number |
04670701
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Psychiatric science
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Research Institution | OKAYAMA UNIVERSITY |
Principal Investigator |
OKAMOTO Motoi Okayama University, School of Health Sciences, Assistant Professor, 医療技術短期大学部, 助教授 (80144757)
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Co-Investigator(Kenkyū-buntansha) |
MORI Shuji Okayama University, School of Health Sciences, Assistant, 医療技術短期大学部, 助手 (50220009)
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Project Period (FY) |
1992 – 1993
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Keywords | cell death / excitatory amino acids / cell culture / cortical neuron / proteoglycan / chondroitin sulfate / heparan sulfate / ELISA |
Research Abstract |
In this project, we established an in vitro model system for studying the mechanism of neuronal death by using primary cultured rat's cortical neurons, and examined the effects of extracellular matrix molecules on the cell death induced by excitatory amino acids. 1)The death of primary cultured cortical neurons of rat fetuses increased in parallel with developmental stage in vivo, providing the fact that primary cultured neurons can be a in vitro model for investing developmental changes of neuronal sensitivity to excitatory amino acids. 2)Chondroitin sulfate proteoglycans (CSPG)prepared from neonatal rat's brain protected neuronal death induced by 24 h exposure to glutamate. 3)The protective effect of CSPG was due to its core protein, but not due to glycosaminoglycan side chains nor adsorption of glutamate. 4)The protective action of CSPG was comparable to a NMDA antagonist, MK-801, and was stronger than AMPA antagonist, NBQX. 5)CSPG also protected delayd neuronal death following 10 min. exposure to glutamate, as well as kainate, NMDA,and AMPA. 6)A enzyme-linked immunosolvent assay for measuring nanogram level of heparan sulfate proteoglycan was established by using lipoprotein lipase (LPL) and anti-LPL rabbit's serum. Based on these findings, we suggested a possible involvement of CSPG in the neuronal death in acute pathological conditions such as ischemia, hypoxia and in chronic degenerative diseases.
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