Cyte-physiological study of abnormal Ca^<2+> metabolism in delayed neuronal death

迟发性神经元死亡中Ca^<2>代谢异常的细胞生理学研究

• 批准号: 15591543
• 负责人: OGURO Keiji
• 金额: $ 2.24万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591543/
• 关键词: cerebral ischemia; calcium; hippocampus; resistance; slice; GluR2; IP_4

Ischemic resistance of developing gerbilsTo investigate the mechanisms by which developing animals exhibit ischemic resistance, we examined the changes in intracellular calcium ([Ca^<2+>]i) after oxygen-glucose deprivation (OGD) using hippocampal slices form gerbils. We found that increases in [Ca^<2+>]i in hippocampal CA1 neurons is significantly less after OGD in developing gerbils than in adults. We then examined the expression of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptors (AMPARs) GluR1-4 during the developmental period by Western blot analysis. We also investigated the anti-apoptotic proteins HSP70,Bcl-XL and plasma membrane Ca^<2+>-ATPase type 1 (PMCA1). GluR2 expression, but not that of the other AMPARs, is significantly higher in developing gerbils than in adults. These results suggest that the higher expression of GluR2 is important for the smaller increases in [Ca^<2+>]i and enhanced resistance to ischemia-induced neuronal damage in developing anim … More als.Functional changes in IP_33 kinase knock-out miceIP_33-kinase metabolizes IP_3 to 1,3,4,5-tetrakisphosphate (IP_4). Until recently physiological roles of IP_33-kinase or IP_4 are not well known. IP_33-kinase (A) is abundant in neuronal cells and IP_4 level in IP_33-kinase(A) deficient mice is significantly decreased. To know the role of IP_33-kinase or IP_4 in neuronal tissue, histochemical, behavioral and physiological study were performed using IP_33-kinase(A) deficient and wild type mice. In histochemical study with IP_33-kinase antibody, IP_33-kinase strongly express in hioppocampal CA1 region in normal gerbil. Passive avoidance with electric shocking chamber revealed less learning and memory function in IP_33-kinase(A) deficient mice. Hippocampal damage induced by global ischemia by 10 min common carotid occlusion did not show significant differences between IP_33-kinase(A) deficient and wild type mice. Intracellular Ca^<2+> increase following oxygen-glucose deprivation was also examined using hippocampal slice of deficient and wild type mice. These results suggest that IP_33-kinase and IP_4 have important roles in the process of learning and memory. Less

发育期沙鼠的抗缺血性为了研究发育期动物表现出抗缺血性的机制，我们用沙土鼠海马脑片检测了氧-糖剥夺（OGD）后细胞内钙（[Ca^2+]i）的变化。我们发现，发育中的沙鼠在OGD后海马CA 1神经元中[Ca^<2+>]i的增加明显低于成年沙鼠。然后我们用Western blot分析了AMPA（α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid）受体（AMPARs）GluR 1 -4在发育过程中的表达。我们还研究了抗凋亡蛋白HSP 70、Bcl-XL和质膜Ca^<2+>-ATPase 1型（PMCA 1）。GluR 2的表达，而不是其他AMPAR，是显着高于在成年沙鼠的发展。这些结果表明，GluR 2的高表达对于[Ca^<2+>]i的较小增加和增强发育中动物对缺血诱导的神经元损伤的抵抗力是重要的。 ...更多信息 IP_33激酶基因敲除小鼠的功能变化IP_33激酶将IP_3代谢为1，3，4，5-四磷酸（IP_4）。直到最近，IP_33-激酶或IP_4的生理作用还不是很清楚。IP_33-激酶（A）在神经细胞中含量丰富，IP_33-激酶（A）缺陷小鼠的IP_4水平显著降低。为了解IP_33-激酶（A）和IP_4在神经组织中的作用，本实验采用IP_33-激酶（A）缺陷小鼠和野生型小鼠，进行了组织化学、行为学和生理学研究。用IP_33-激酶抗体进行组织化学染色，结果显示IP_33-激酶在正常沙土鼠海马CA 1区有强表达。IP_33-kinase（A）基因缺陷小鼠的学习记忆功能明显下降。IP_33-激酶（A）缺陷型小鼠和野生型小鼠的全脑缺血10分钟诱导的海马损伤没有显示出显著差异。我们还用缺糖小鼠和野生型小鼠的海马切片检测了缺氧缺糖后细胞内Ca^<2+>的增加。提示IP_33激酶和IP_4在学习记忆过程中起重要作用。少

项目成果

虚血性神経細胞死とギャップ結合in脳血管障害による「神経細胞死」の予防と治療(川合述史編)

脑血管疾病引起的缺血性神经元死亡和“神经元死亡”中间隙连接的预防和治疗（河合正史编辑）

• 发表时间: 2003
• 作者: 小黒恵司;田中秀信;横田英典;宮脇貴裕
• 通讯作者: 宮脇貴裕

Oguro K, Miyawaki T, Yokota H, Kato, M, Watanabe M, Shimazaki K, et al.: "Upregulation of GluR2 decreases intracellular Ca^<2+> following ischemia in developing gerbils"Neurosci.Letter. (in press). (2004)

Oguro K、Miyawaki T、Yokota H、Kato, M、Watanabe M、Shimazaki K 等人：“GluR2 的上调可减少发育中沙鼠缺血后的细胞内 Ca^2””Neurosci.Letter。

Ischemic neuronal death and gap junctions.

缺血性神经元死亡和间隙连接。

• 发表时间: 2003
• 期刊: Prevention and therapy for neuronal death by cerebrovascular disease (Kawai N ed.) Tokyo
• 作者: Oguro K;Tanaka H;Yokota H;Miyawaki T.
• 通讯作者: Miyawaki T.

Ischemic tolerance with 3-nitropionic acid induces the over expression of Bcl-2 and Bcl-_<XL> but lacking for HSP70 and plasma membrane Ca^<2+>-ATPase type 1.

3-硝基丙酸的缺血耐受诱导 Bcl-2 和 Bcl-_<XL> 过度表达，但缺乏 HSP70 和质膜 Ca^2-ATPase 1 型。

• 发表时间: 2005
• 期刊: Life Science (in press)
• 作者: Kato K;Shimazaki K;Kamiya T;Amemiya S;Inaba T;Oguro K;Katayama Y.
• 通讯作者: Katayama Y.

Upregulation of GluR2 decreases intracellular Ca2+ following ischemia in developing gerbils.

发育中的沙鼠缺血后，GluR2 的上调会减少细胞内 Ca2+。

• 发表时间: 2004
• 期刊: Neurosci Letters 364
• 作者: Oguro K;Miyawaki T;Hokota H;Kato K;Kamiya T;Katayama Y;Fukaya M;Watanabe M;Shimazaki K.
• 通讯作者: Shimazaki K.