Neurophysiological examination in relationship of glaucomatous neurodegeneration and glutamate neurotoxicity

青光眼神经变性与谷氨酸神经毒性关系的神经生理学检查

• 批准号: 07671921
• 负责人: MISHIMA Hiromu
• 金额: $ 1.34万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671921/
• 关键词: 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

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.

在1995年，我们发现，与PKC相关药物的激活症状磷脂信号传导途径恶化，并通过血管活性肠肽（VIP）改善护性的谷氨酸神经毒性激活腺苷酸性神经酶。在1996年，我们通过图像分析系统和全细胞贴剂钳记录的向内电流来检查胞质Ca^<2+>浓度的动力学（[Ca^<2+>] i），以阐明PKC相关药物对谷氨酸毒性毒素的影响的机制。使用上面提到的这些程序，这些药物对谷氨酸诱导的[Ca^<2+>] I或谷氨酸诱导的内向电流的增加没有影响。因此，我们推测与PKC相关的药物和VIP影响了谷氨酸受体受体激活下游的谷氨酸神经毒性的机制。我们发现，细胞外环境从pH 7.4转变为酸性条件（pH 6.0-7.0）受培养的培养性视网膜神经蛋白神经毒性神经毒性神经毒性神经毒性（pH 6.0-7.0）。在使用斑块钳记录的电生理检查中，N-甲基-D-天冬氨酸（NMDA）受体激活被抑制了细胞外酸性pH。

项目成果

Kosaka T., Mishima H.K., Kiuchi Y., Kataoka K.: "Effects of prostaglandins on the blood-ocular barrier." Jpn.J.Ophthalmol.39. 368-376 (1995)

Kosaka T.、Mishima H.K.、Kiuchi Y.、Kataoka K.：“前列腺素对血眼屏障的影响。”

Mishima H.K.: "Effects of prostaglandins on the blood-ocular barrier." Japanese Journal of Ophthalmology. 39. 368-376 (1995)

Mishima H.K.：“前列腺素对血眼屏障的影响。”

Mishima H.K.: "Ultrasound biomicroscopic study of ciliary body thicknesess of pharmacologic agents." American Journal of Ophthalmology. 121. 319-321 (1996)

Mishima H.K.：“药物制剂睫状体厚度的超声生物显微镜研究”。

Mishima H.K.: "Ca^<2+>/calmodulin effects on cAMP response in cultured chick ciliary epithelial cells." Japanese Journal of Ophthalmology. 39. 317-322 (1995)

Mishima H.K.：“Ca ^ 2 /钙调蛋白对培养的鸡睫状上皮细胞中cAMP反应的影响。”

Mishima H. K.: "Ultrasound biomicroscopic study of ciliary body thickness of pharmacologic agents" American Journal of Ophthalmology. 121. 319-321 (1996)

Mishima H.K.：“药物制剂睫状体厚度的超声生物显微镜研究”美国眼科杂志。