小鼠海马内HDAC2的表达及其与NMDA受体、PSD-95的共定位

摘要

Objective To investigate the distribution of histone deacetylase 2 (HDAC2) in the hippocampus of adult C57BL/6 mice and the co-localizations of HDAC2 and PSD components, such as N-methyl-D-aspartate (NMDA) receptor 1 (NR1) and PSD-95, and provide morphological evidence for inherent relationship between postsynaptic density (PSD) components in synapses and HDAC2 in nucleus. Methods The morphology and distribution of HDAC2 positive neurons in the hippocampus were observed by immunohistochemistry. The hippocampal distributions of NR1 and PSD-95, as well as co-location with HDAC2 were detected using double immunofluorescence staining. Results HDAC2 immunoreactivity was mainly observed in hippocampal CA1-CA3 pyramidal cells and dentate gyros granule cells. The scattered positive cells were accidentally present in the oriens layer, radiate layer and lacunosum-moleculare layer of CA1-CA3 and molecular layer and polymorphic layer of dentate gyrus. The distributions of NR1 and PSD-95 positive neurons are similar to that of HDAC2 positive neurons in the hippocampus. The co-location analysis showed that almost all HDAC2 immunoreactive neurons observed in pyramidal cells of CA1-CA3 and granule cells of dentate gyrus. Conclusions HDAC2 is rich in hippocampal pyramidal cell layer and granule cell layer, and co-located with PSD proteins. The results provide a morphological clue to explain the role of HDAC2 in postsynaptic glutamatergic neuron-dependent synaptic plasticity.%目的 探讨组蛋白去乙酰化酶2(HDAC2)在成年C57BL/6小鼠海马内的分布及其与突触后致密区(PSD)蛋白成员的共定位,为揭示HDAC2与PSD蛋白复合物之间的内在联系及在海马相关的学习记忆过程中可能起到的调控作用提供形态学依据.方法 应用免疫组化方法观察HDAC2在C57BL/6小鼠海马各区的表达分布.应用免疫荧光双标技术研究HDAC2与PSD蛋白成员N-甲基-D-天冬氨酸(NMDA)受体亚单位1(NR1)、PSD-95之间是否存在共定位.结果 HDAC2在小鼠海马CA1～CA3区锥体细胞和齿状回颗粒细胞均具有明显表达,而在各区的始层、辐射层、腔隙-分子层以及齿状回多形细胞层表达均较少.免疫荧光双标染色图片的重叠表明,HDAC2与NR1、PSD-95在小鼠海马CA1～CA3区锥体细胞层和齿状回颗粒细胞层内均可见显著共表达现象,其他区域偶见散在分布的双染神经元.结论 HDAC2在小鼠海马锥体细胞层和颗粒细胞层表达丰富,并与PSD蛋白成员间存在共定位现象.本实验结果为探讨HDAC2对谷氨酸能突触后神经元依赖的突触可塑性的调节机制提供了形态学依据.