ApoE4对大鼠在体海马L-LTP的影响及其分子机制的分析

发布时间：2018-07-24 08:26

【摘要】：探讨载脂蛋白E4(apolipoprotein E,apoE4)的神经毒性作用。将12只健康雄性SD大鼠随机分成对照组和实验组两组(n=6)。采用电生理手段,利用海马给药装置和刺激/记录绑定电极记录大鼠在体海马CA1区场兴奋性突触后电位(fEPSP)和高频刺激(HFSs)诱导的晚期长时程增强(L-LTP),观察急性注射apoE4后对大鼠海马CA1区L-LTP的诱导及维持的影响。并且通过Western Blotting检测cAMP应答元件结合蛋白(CREB)的表达及其磷酸化水平,探讨apoE4影响L-LTP的分子机制。结果表明,HFSs前注射0.2μg apoE4并没有改变突触传递,对双脉冲易化(PPF)没有影响。但显著抑制L-LTP的诱导和维持,降低CREB的磷酸化水平。说明apoE4可以损伤海马L-LTP。这种神经毒性不是突触前神经递质释放所介导,而是通过降低突触后CREB活性实现的。
[Abstract]:To investigate the neurotoxicity of apolipoprotein EpoE4 (ApoE4). Twelve healthy male Sprague-Dawley rats were randomly divided into two groups: control group and experimental group. By electrophysiological means, Field excitatory postsynaptic potential (fEPSP) and late long-term potentiation (L-LTP) induced by high frequency stimulation of (HFSs) were recorded by hippocampal administration device and stimulation / record binding electrode in rat hippocampal CA1 region in vivo. The effects of apoE4 on CA1 in hippocampus of rats were observed after acute apoE4 injection. Induction and maintenance of L-LTP. The expression and phosphorylation level of cAMP response element binding protein (CREB) were detected by Western Blotting to explore the molecular mechanism of apoE4 affecting L-LTP. The results showed that pre-injection of 0.2 渭 g apoE4 did not change synaptic transmission, but had no effect on double-pulse facilitation (PPF). But it significantly inhibited the induction and maintenance of L-LTP and decreased the phosphorylation level of CREB. These results suggest that apoE4 can injure L-LTP in hippocampus. This neurotoxicity is not mediated by the release of presynaptic neurotransmitters, but by the reduction of postsynaptic CREB activity.
【作者单位】：山西医科大学基础医学院生理学系细胞生理学教育部重点实验室;
【基金】：国家自然科学基金资助项目(31271201) 山西省自然科学基金资助项目(2009011054-2)
【分类号】：R749.16

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