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KA1表达再分布对神经元兴奋毒性的影响

     

摘要

背景:特异的兴奋性神经递质受体过度活化时便发生细胞的兴奋性中毒,有关NMDA受体和AMPA受体活化致细胞兴奋性中毒死亡通路较为明确,但关于红藻氨酸(Kainate,KA)受体的功能到目前为止仍未明了.目的:探究小鼠海马内注射KA之后KA1受体的再分布状况对中枢神经元兴奋性中毒的影响.方法:成年雄性C57BL6小鼠海马内注射KA或PBS,2 h后进行Bederson体征评分、全脑切片免疫组化分析和死亡神经元检测.结果与结论:海马内注射KA 2 h后,Bederson体征评分表明中枢神经功能出现明显损伤;KA1受体表达的变化主要出现在海马CA1和CA3区,在CA1区的表达上调明显,并开始出现神经元死亡,4~6 h后可见大量神经元死亡.结果表明 KA促使KA1受体亚单位在海马神经元CA区重新分布,增加神经元对兴奋性氨基酸毒性的敏感性,导致神经细胞死亡,中枢神经功能缺失.%BACKGROUND: The excessive activation of the specific excitatory neurotransmitter receptors may lead to cell exitotoxicity, the exitotoxic cell death pathway which is involved in the N-methyl-D-aspartate receptors and a-amino-3-hydroxy-5- methyl-4-isoxazole-propionicacid receptors were clear. However, the function of kainite (KA) receptors is still unclear. OBJECTIVE: To study the effect of the re-distribution of KA receptors after KA injection into the hippocampus of mice on the neuronal exitotoxicity. METHODS: KA or phosphate buffered saline was injected into the hippocampus of adult male C57BL6 mice. Two hours later, the Bederson score analysis, immunohistochemistry brain sections and neuronal death detection were performed. RESULTS AND CONCLUSION: Bederson score showed severe injury of central nervous system function at 2 hours after injection into the hippocampus. The changes of KA1 receptor expression were mainly in the hippocampal CA1 and CA3 region Obvious up-regulation of KA1 receptor expression and neuronal cell death were mainly in the CA1 region, and abundant cell death could be seen 4-6 hours later. KA can promote the re-distribution of KA1 receptor subunit in the CA region of the hippocampus and increase the excitatory amino acid toxicity of neuron resulted in neuronal cell death and disfunction of the central nervous system.

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