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作 者:刘赞华[1] 廉春燕 李淑敏[1] 赵红[1] 王苏平[1]
机构地区:[1]大连医科大学附属大连市中心医院神经内一科,116033
出 处:《中国临床神经科学》2016年第2期153-157,165,共6页Chinese Journal of Clinical Neurosciences
基 金:大连市医学科学研究计划项目(编号:0205302201)
摘 要:目的探讨精神发育迟滞相关基因CDKL3失活对侧脑室旁区细胞增殖的影响,揭示CDKL3相关精神发育迟滞的病理机制。方法将体外培养的原代海马神经元随机分为细胞敲减1组、细胞敲减2组、细胞敲减3组和细胞对照组,采用质粒细胞电转法干扰各组神经元中CDKL3基因表达,采用Western blot法验证基因干扰质粒的效率。将小鼠胚胎随机分为胚胎敲减1组、胚胎敲减2组、胚胎敲减3组和胚胎对照组,采用质粒胚胎电转法干扰各组活体小鼠侧脑室旁区细胞中CDKL3基因表达,采用免疫荧光组化法及荧光共聚焦显微成像技术检测各组侧脑室旁区脑组织单位体积中增殖细胞/总细胞的百分比。结果敲减侧脑室旁区细胞中的CDKL3可导致侧脑室旁区的GFP-Brd U-Hoechst共标细胞/GFP阳性细胞百分比显著下降。结论 CDLK3失活可抑制富含神经前体细胞的侧脑室旁区的细胞增殖,影响皮质神经元的数量,参与非特异性精神发育迟滞的病理过程。Aim To study the effect of CDKL3 inactivation on the proliferation of cells at the ventricular zone/subventricular zone in the brain and reveal the underlying relationship between CDKL3 inactivation and non-syndromic mild mental retardation.Methods The hippocampal neurons in vitro were randomly divided into knocked-down group 1, 2, 3 and a control group,then verified the efficiency of plasmid RNAi by the method of Western blot. The effect of CDKL3 inactivation on the proliferation of cells at the vz/svz in vivo were studied by the method of RNA interference, in utero electroporation and immunofluorescence. Results CDKL3-deficient mouse exhibited a statistical significant reduction in the percentage of GFPBrd U-Hoechst colabeled neurons/GFP-positive cells. Conclusion CDKL3 inactivation mild inhibited the proliferation of cells at the the ventricular zone/subventricular zone, where a great number of neural progenitor cells were located, and CDKL3 inactivation may be contribute to non-syndromic mentalretardation by affecting the proliferation of neural progenitor cells at the ventricular zone/subventricular zone during the crucial development stages of the central nerve system.
分 类 号:R749.93[医药卫生—神经病学与精神病学] Q189[医药卫生—临床医学]
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