海马Cajal-Retzius细胞的正常发育及在APPswe转基因小鼠中的改变

目的 观察reelin阳性Cajal-Retzius细胞（CR细胞）在正常小鼠及APPswe转基因小鼠海马发育中的变化，探讨CR细胞在阿尔茨海默病（AD）发生发展过程中所起的作用，为研究AD发病机制和临床治疗提供新的思路和方法。 方法 80只实验小鼠分为APPswe转基因模型组和对照组，每一组内分E16、P0、P7 、P15 、P30、P90、P180和P360 8个年龄段，每一年龄段小鼠各取5只。另取12月龄模型组和对照组小鼠各3只，用硫黄素S染色技术检测APPswe转基因小鼠脑内沉积的老年斑；免疫荧光技术标记正常及模型组小鼠齿状回分子层内reelin阳性CR细胞，同时采用谷氨酸、γ氨基丁酸(GABA)、活化型Caspase-3分别与reelin双重标记以研究CR细胞的组织化学特点及凋亡情况；最后利用免疫印迹方法对海马组织内reelin的活化片段进行半定量分析。 结果 随着海马发育CR细胞逐渐减少，不同时期的reelin阳性CR细胞可以分别被谷氨酸、GABA、Caspase-3标记；APPswe转基因小鼠海马内CR细胞的数量明显少于正常对照组，免疫印迹法结果与免疫细胞化学统计结果吻合。 结论 出生后CR细胞的丢失是由于凋亡所致，在海马发育的不同时期CR细胞分泌兴奋性或抑制性神经递质，以此来调节突触间的信息传递与突触可塑性。APPswe转基因小鼠海马内CR细胞低于正常对照组，提示CR细胞丢失可能与AD相关的神经元退行性病变有关。

Normal development of Cajal-Retzius cells in mouse hippocampus and their changes in APPswe transgenic mice

Objective In order to compare the alteration of reelin-immunoreactive Cajal-Retzius cells (CR cells) in molecular layer of dentate gyrus of APPswe transgenic mice with wild type, the histochemical and developmental characteristics of CR cells were studied, therefore, the roles of CR cells in Alzheimer's disease would be revealed further.Methods The Thioflavine S staining, reelin immunofluorescence with or without reelin/glutamate and reelin/GABA immuno-double staining were carried out in the study. In the meantime, Western blotting was used to study the expression of reelin in hippocampi of the both wild type and transgenic mice. Results Reelin positive CR cells could be double-labeled with either glutamate or GABA immunostaining. Caspase-3 immunofluorescence demonstrated that some CR cells went through apoptosis during their development. Compared with wild type, CR cells in APPswe transgenic mice had significantly decreased in the molecular layer of the dentate gyrus. The result was supported with Western blotting analysis of reelin expression in hippocampus. Conclusion Reelin could be co-expressed with either glutamate or GABA, suggesting CR cells would be glutamatergic exciting neurons and GABAergic interneurons. The loss of CR cells during development probably was caused by the neuroapoptosis. Significant decrease of CR cells in hippocampus of APPswe transgenic mice indicated reelin may play an important role in AD pathological alterations.