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

为了探讨发育中的沙鼠出现缺血抵抗的机制，我们利用沙鼠海马切片检测了氧葡萄糖剥夺（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CA1神经元中[Ca^<2+>]i的增加明显少于成年沙鼠。Western blot检测发育期间AMPA （α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸）受体GluR1-4的表达。我们还研究了抗凋亡蛋白HSP70、Bcl-XL和质膜Ca^<2+>-ATPase 1型（PMCA1）。发育中的沙鼠中GluR2的表达明显高于成年沙鼠，而其他AMPARs的表达则不同。这些结果表明，GluR2的高表达对于发育动物[Ca^<2+>]i的较小增加和对缺血诱导的神经元损伤的增强具有重要意义。IP_33激酶敲除小鼠eip_33激酶代谢IP_3为1,3,4,5-四磷酸（IP_4）的功能改变。直到最近ip333激酶或IP_4的生理作用还不为人所知。神经元细胞中ip333激酶(A)含量丰富，ip333激酶(A)缺陷小鼠IP_4水平明显降低。为了了解ip333激酶或IP_4在神经元组织中的作用，我们对ip333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ip333激酶抗体进行组织化学研究，发现ip333激酶在正常沙鼠海马CA1区强表达。ip333激酶(A)缺陷小鼠的学习记忆功能明显下降。ip333激酶(A)缺陷小鼠与野生型小鼠相比，颈总动脉闭塞10 min引起的海马缺血损伤无显著差异。缺氧型和野生型小鼠的海马切片也检测了缺氧后细胞内Ca^<2+>的升高。提示ip333激酶和IP_4在学习记忆过程中起重要作用。少

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