NSCs移植对AD鼠基底前脑胆碱能神经元和学习记忆能力的影响

Effects of NSCs transplantation on cholinergic neurons of basal forebrain and abilities of learning and memory in AD rats

目的:探讨神经干细胞(NSCs)移植对侧脑室注射192-IgG-saporin致老年性痴呆(AD)动物模型的治疗作用。方法:24只SD大鼠随机分为正常组,模型组和移植组,每组8只。左侧侧脑室注射192-IgG-saporin5μ(l0.5μg/μl),建立AD动物模型,基底前脑行NSCs移植,Y-迷宫行为检测,NADPH-d组织化学法染色,结合图像分析技术观察各组大鼠基底前脑NOS阳性神经元数目和形态学参数的变化。结果:侧脑室注射192-IgG-saporin1个月,损伤侧基底前脑内侧隔核(MS)和斜角带垂直支(VDB)一氧化氮合酶(NOS)阳性神经元数明显减少,分别减少到正常组的22.43%和28.36%(与正常组相比P<0.01)。移植组NOS阳性神经元数恢复到正常组的70.22%和74.88%(与模型组相比P<0.01)。细胞形态学参数提示,移植组NOS阳性神经元中含有大小不等的未成熟细胞。大鼠的学习记忆能力与基底前脑NOS阳性细胞数呈正相关。结论:NSCs移植对注射192-IgG-saporin致AD鼠基底前脑胆碱能神经元有明显补充和保护作用,可改善大鼠的学习记忆能力。

Objective： To explore the effects of the transplantation of neural stem cells on cholinergic neurons of basal forebrain and abilities of learning and memory in AD rats obtained by 192-IgG-saporin treatment. Methods： 24 adult SD rats were randomly divided into three groups： normal group, model group and grafting group, with 8 rats in each group. 192-IgG-saporin （2.5μg/5μl） was unilaterally injected into the lateral ventricle of animals for establishing AD animal model. Rats performed with the selective imrnunotoxin 192-IgG-saporin received neural stem cells transplantation in basal forebrain. 4 weeks after surgery, morphologic data and percentages of NOS-positive neurons were measured in basal forebrain by using NADPH-d histochemical method combined with technique of micromeasure and image analysis. Learning and memory abilities were measured by Y-maze test. Results： About 1 month after 192-IgG-saporin injecting, 22.43% and 28.36% of NOS-positive neurons appeared in medial septum （MS） and vertical diagonal band （VDB） of the lesion side of basal forcbrain （P〈0.01 ,compared with the normal group）. After the transplantation of NSCs, 70.22%/74.88% of NOS-positive neurons survived in MS / VDB （P〈0.01,compared with the model group）. Morphologic data of NOS-positive neurons indicated that there were some premature cells among them in grafting group. The abilities of learning and memory were significantly related with the number ofcholinergic neurons. Conclusions： The results suggest that NOS-positive neurons in MS and VDB of basal forebrain of AD rats can be renewed and protected and improved the ability of spatial learning and memory in model rats with Alzheimer＇s disease after treatment with neural stem cells.