Cytephysiological investigation for abnormal Ca^<2+> metabolism in delayed neuronal death

IP_33kinase敲除小鼠的功能变化为了研究IP4在正常和病理状态下的作用，我们用IP_33kinase敲除小鼠进行了实验。双侧颈总动脉闭塞10 min对全身缺血的易损性，在病理研究中没有发现敲除小鼠和萎缩性颈内动脉型小鼠的差异。氧糖剥夺诱导的海马片Rhod2显像钙升高也无差异。在被动回避实验中，IP_33kinase敲除小鼠表现出明显较差的结果。这些结果表明IP4在保持记忆方面有一定的作用。间隙连接蛋白Cx（连接蛋白）32（由少突胶质细胞和/或中间神经元表达）、Cx36（由中间神经元和部分锥体神经元表达）和Cx43（由星形胶质细胞表达）在小鼠全脑缺血后海马神经元死亡的细胞特异性模式中发挥作用。Northern blot和原位杂交检测发现，缺血未显著改变易感CA1中Cx32、Cx36和Cx43 mRNA的表达。Western blot分析显示，在神经元死亡发生前，全脑缺血诱导CA1中Cx32和Cx36蛋白丰度选择性增加，而Cx43蛋白丰度不增加。双免疫荧光检测显示，Cx32和Cx36的表达增加发生在海马CA1的palvalbumine阳性抑制性中间神经元中。CA3和齿状回中这三种连接蛋白的丰度在所有时间检测时都没有变化。连接蛋白在没有相应mrna变化的情况下发生变化，这一发现与Cx32和Cx36在翻译和/或翻译后水平的表达调控是一致的。Cx32 （Y/）缺失小鼠对短暂缺血损伤的易感性增强，这与Cx32间隙连接在神经元存活中的作用一致。这些发现提示了Cx32和Cx36间隙连接促进gaba能中间神经元存活和抵抗的机制，从而定义了细胞特异性的全局缺血诱导的神经元死亡模式。少

Functional changes in IP_33kinase knock-out miceTo investigate the role of IP4 in the normal or the pathological conditions, we performed experiments using IP_33kinase knock-out mice. The vulnerability to global ischemia by 10 min bilateral common carotid occlusion, no differences was detected in pathological study between knock-out mice and the wilt type. Calcium increase in Rhod2 imaging induced by oxygen-glucose deprivation on hippocampal slice also showed no differences. In passive avoidance test IP_33kinase knock-out mice showed significantly poorer results. These results suggest that IP4 plays some role in keeping memory.The role of gap junction in cerebral ischemiaThe present study was undertaken to examine the hypothesis that the gap junctional proteins Cx (connexin) 32 (expressed by oligodendrocytes and/or interneurons), Cx36 (expressed by interneurons and some pyramidal neurons) and Cx43 (expressed by astrocytes) play a role in defining cell-specific patterns of neuronal deat … More h in the hippocampus after global ischemia in mice. Global ischemia did not significantly alter Cx32, Cx36 and Cx43 mRNA expression in the vulnerable CA1, as assessed by Northern blot analysis and in situ hybridization. Global ischemia induced a selective increase in Cx32 and Cx36, but not Cx43, protein abundance in CA1 prior to the onset of neuronal death, as assessed by Western blot analysis. The increase in Cx32 and Cx36 expression was in palvalbumine positive inhibitory interneurons of the hippocampal CA1, as assessed by double immunofluorescence. Abundance of the three connexin proteins was unchanged in CA3 and dentate gyrus at all times examined. The finding that connexin proteins change in the absence of a change in the corresponding mRNAs is consistent with the regulation of Cx32 and Cx36 expression at the translational and/or post-translational levels. Cx32 (Y/) null mice exhibited enhanced vulnerability to brief ischemic insults, consistent with a role for Cx32 gap junctions in neuronal survival. These findings suggest a mechanism by which Cx32 and Cx36 gap junctions contribute to the survival and resistance of GABAergic interneurons, thereby defining cell-specific patterns of global ischemia-induced neuronal death. Less