Presenilins条件性双基因敲除小鼠海马与皮层超微结构的增龄性变化

发布时间：2018-04-23 21:32

本文选题：Presenilins + 条件性双基因敲除小鼠　；参考：《复旦学报(自然科学版)》2013年04期

【摘要】：为研究Presenilins条件性双基因敲除对于小鼠海马与皮层超微结构的影响,选用3、6及12月龄Presenilins 1/Presenilins 2双敲除小鼠(dKO)和同窝对照小鼠(CON),运用透射电子显微镜技术,分别观察海马与皮层突触、细胞核、线粒体、溶酶体超微结构的改变.结果发现:3月龄dKO小鼠海马与皮层溶酶体已向次级溶酶体转化.6月龄dKO小鼠海马与皮层的突触后致密物厚度显著降低;皮层细胞核膜内陷,核不规则;海马与皮层线粒体出现肿胀、嵴变形或消失;出现高电子密度的次级溶酶体,并伴有脂褐素小体出现.12月龄dKO小鼠海马与皮层突触后致密物厚度显著减小,突触间隙宽度显著增加;海马与皮层核膜内陷,染色质固缩沿核膜分布;线粒体严重受损,嵴大部分溶解;出现较多次级溶酶体和脂褐素小体.Presenilins条件性双基因敲除对小鼠海马与皮层有增龄性的病理影响,这些病理改变将为相关的药物评价和对阿尔茨海默病的深入研究提供形态学依据.
[Abstract]:In order to study the effect of Presenilins conditioned double gene knockout on the ultrastructure of hippocampus and cortex in mice, the synapses of hippocampus and cortex were observed by transmission electron microscopy (TEM) in Presenilins 1/Presenilins 2 double knockout mice aged 3 and 12 months. Ultrastructural changes of nucleus, mitochondria and lysosomes. The results showed that the thickness of postsynaptic dense substance in hippocampus and cortex of dKO mice at the age of 3 months was significantly lower than that of dKO mice at the age of 6 months, and the nucleus of cortex was irregular, and the thickness of postsynaptic dense substance in hippocampus and cortex of dKO mice was significantly decreased. Mitochondria of hippocampus and cortex were swollen, cristae deformed or disappeared, secondary lysosomes with high electron density and lipofuscin bodies appeared in dKO mice of 12 months old, the thickness of postsynaptic dense substance in hippocampus and cortex decreased significantly. The width of synaptic space was significantly increased, the nuclear membrane of hippocampus and cortex was trapped, the chromatin pyknosis was distributed along the nuclear membrane, the mitochondria was seriously damaged and most of the cristae were dissolved. There were more secondary lysosomes and lipofuscin bodies. Presenilins conditional double gene knockout had an aging effect on hippocampus and cortex of mice. These pathological changes will provide morphological basis for drug evaluation and further study of Alzheimer's disease.
【作者单位】：华东师范大学生命科学学院;华东师范大学脑功能基因组学重点实验室;
【基金】：上海市科委重点项目(10JC1411200)
【分类号】：R338

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