1999 Fiscal Year Final Research Report Summary
A study of hypoxic oligodendroglial injury
| Project/Area Number |
10670611
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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 |
Neurology
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
YOSHIOKA Akira Neurology, Associate Professor, 医学部・神経内科, 助教授 (80182723)
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| Project Period (FY) |
1998 – 1999
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| Keywords | oligodendroglia / hypoxia / cell death / exctitotoxicity / cyclic AMP / cyclic GMP / Na+ / Ca2+exchanger |
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| Research Abstract |
Previously, we have found that CaィイD12+ィエD1 accumulation via non-N-methyl-D-aspartate (NMDA) glutamate receptor (GluR) mediates oxygen-glucose deprivation induced oligodendroglial injury. In the present study, we investigated the mechanism of CaィイD12+ィエD1 accumulation when non-NMDA GluR are activated in oligodendroglial cells. Oligodendroglial cells express mRNAs encoding each of the three known NaィイD1+ィエD1-CaィイD12+ィエD1 exchanger isoforms. Kainate-induced oligodendroglial CaィイD12+ィエD1 accumulation is dimished by replacement of extracellular NaィイD1+ィエD1 with N-methyl-D-glucamine, and by the NaィイD1+ィエD1-CaィイD12+ィエD1 exchanger blockers, 3, 4-dichlorobenzamil (DCB) and benzamil. These results indicate that kainate-induced CaィイD12+ィエD1 accumulation results, at least in part, from NaィイD1+ィエD1-CaィイD12+ィエD1-mediated exchange of intracellular NaィイD1+ィエD1 for extracellular CaィイD12+ィエD1. We previously found that agents which elevate intracellular cAMP or cGMP inhibit kainate-induced CaィイD12+ィエD1 accumulation and prevent kainate induced excitotoxicity. To test the hypothesis that cAMP and cGMP inhibit "reverse" mode operation of NaィイD1+ィエD1-CaィイD12+ィエD1 exchangers, we loaded oligodendroglia with NAィイD1+ィエD1 in the absence of quaint by incubation with veratridine and ouabain in an NaィイD1+ィエD1 containing medium. This caused CaィイD12+ィエD1 accumulation, which was inhibited by agents that elevate intracellular cMAP or cGMP prevent oxygen-glucose deprivation-induced oligodendroglial injury by inhibiting "reverse" mode operation of NaィイD1+ィエD1-CaィイD12+ィエD1 exchangers.
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Research Products
(10 results)
