Neurophysiological examination in relationship of glaucomatous neurodegeneration and glutamate neurotoxicity
| Project/Area Number |
07671921
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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 |
Ophthalmology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
MISHIMA Hiromu Hiroshima Univ.Sch.of Med.Professor, 医学部, 教授 (20034100)
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| Co-Investigator(Kenkyū-buntansha) |
KOSAKA Toshiya Hiroshima Univ.Med.Hosoital.Research Associate, 医学部・附属病院, 助手 (50253084)
木内 良明 広島大学, 医学部, 助手 (40214738)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Retinal culture / Neuronal death / Glutamate / Calcium ion / Patch-clamp / Acidosis / プロテインキナーゼC / 血管作動性腸管ペプチド |
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| Research Abstract |
In 1995, we found that the activation of inositol phospholipid signaling pathway by PKC-related drugs deteriorated and the activation of adenylyl cyclase by vasoactive intestinal peptide (VIP) ameliorated glutamate neurotoxicity in retinal cultures. In 1996, we examined the dynamics of cytosolic Ca^<2+> concentration ([Ca^<2+>] i) by image analyzing system and the glutamate-induced inward current by whole-cell patch-clamp recordings, respectively, to elucidate the mechanisms of the effect of PKC-related drugs or VIP on glutamate-neurotoxicity. Using these procedure mentioned above, these drugs had no effect on glutamate-induced increase in [Ca^<2+>] i or glutamate-induced inward currents. Therefore, we speculated that PKC-related drugs and VIP affected the mechanisms of glutamate neurotoxicity at the downstream of glutamate receptor-activation.
Furthermore, we found that the change of extracellular environment from pH 7.4 to acidic conditions (pH 6.0-7.0) protected cultured retinal neurons from glutamate neurotoxicity. In the electrophysiological examination using patch-clamp recording, N-methyl-D-aspartate (NMDA) receptor-activation was inhibited by extracellular acidic pH.Taken together, the acidic conditions protected cultured retinal neurons from glutamate neurotoxicity via suppression of NMDA receptor-activation.
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Report
(3 results)
Research Products
(16 results)
