noggin基因修饰神经干细胞移植对衰老小鼠学习记忆能力的改善

本研究旨在探讨重组腺病毒介导的noggin基因修饰的小鼠神经干细胞(NSCs)移植入D-半乳糖致衰小鼠海马后的迁移及对小鼠学习记忆能力的影响。分别以含noggin基因的重组腺病毒(pAdEasy-1-noggin-GFP)及对照病毒(pAdEasy-1-GFP)转染体外培养的NSCs,获取神经干细胞克隆(NSCs-noggin;NSCs-GFP),移植入由D-半乳糖诱导的衰老模型小鼠右侧海马CA3区,术后4周采用Y-电迷宫检测小鼠的学习记忆行为,并对各组小鼠脑组织海马段行石蜡冠状切片、免疫组织化学和BrdU免疫荧光化学方法检测。结果显示:基因修饰的NSCs移植对小鼠的学习记忆行为的改善比pAdEasy-1-GFP组更为明显,其记忆保持率持续时间更长;NSCs移植后能在宿主海马内迁移,基因修饰的NSCs移植组在海马内的BrdU阳性细胞数较多(P<0.05)。以上结果表明noggin基因不但可能参与衰老小鼠的学习记忆行为,而且能够促进NSCs的迁移。

LEARNING AND MEMORY AMELIORATION AFTER TRANSPLANTATION OF THE NEURAL STEM CELLS MODIFIED WITH NOGGIN GENE ON AGING MICE

The present study aims to investigate the survival,migration of the neural stem cells(NSCs) and the learning and memory amelioration of aging mice induced by D-galactose after transplantation of NSCs with or without modification by recombinant adenovirus of mouse noggin gene.The NSCs were incubated in pAdEasy-1-noggin-GFP and pAdEasy-1-GFP recombinant adenoviral supernatant in vivo,respectively,and the NSCs-noggin and NSCs-GFP colonies were achieved,and transplantated to the CA3 of right hippocampus of the aging mice induced by D-galactose.Four weeks later,the mice underwent behavioral test of Y-maze.Routine paraffin was made in coronal sections of hippocampus region and immunohistochemistry and immunofluorescence for BrdU were conducted.The results showed that the learning and memory ability of mice grafted with noggin-transduced NSCs was much better ameliorated compared with mice grafted with pAdEasy-1-GFP.In addition,both NSCs were migrated into subregions of hippocampus,but the number of BrdU-positive cells in noggin group was more than that of GFP group(P<0.05).In conclusion,the noggin-transduced NSCs graft provides amelioration of learning and memory of aging mice and the NSCs capable of producing noggin can survive and function better in the brain.