【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.更多还原

【Abstract】 To investigate the ultrastructural changes in the hippocampus and cortex of Presenilins conditional double knockout(dKO) mice,3-,6-and 9-month-old dKO and control mice were included in this study.The ultrastructure of synapse,nuclear,mitochondria and lysosomes were detected by using the transmission electron microscope(TEM).The lysosomes slightly swelled in hippocampus and cortex of dKO mice at 3 months.At 6 months,the thickness of postsynaptic density(PSD) in hippocampus and cortex of dKO mice decreased significantly.TEM observation showed nuclear membranes retraction and irregular nuclear form in cortex of dKO mice.The mitochondria also slightly collapse in hippocampus and cortex of dKO mice;and some swelling lysosomes which contain high electron density and lipofuscin bodies appeared in hippocampus and cortex of dKO mice at 6 months.At 12 months,not only the thickness of PSD decreased significantly,but also the synaptic space width increased significantly in hippocampus and cortex of dKO mice.TEM observation showed nuclear membrane retraction and condensation of chromatin in hippocampus and cortex of dKO mice.The mitochondria collapsed seriously with a wide range of solubility in hippocampus and cortex of dKO mice.Many swelling lysosomes which contain high electron density and ipofuscin bodies appeared in hippocampus and cortex of dKO mice.These results indicated Presenilins conditional knockout has age-related pathology effects on hippocampus and cortex.These pathological changes will provide the evidences for drug evaluation and further research of Alzheimer’s disease.更多还原