神经干细胞移植对老年痴呆模型鼠基底前脑胆碱能神经元和学习记忆能力的影响  

The effects of neural stem cell transplantation on cholinergic neurons of the basal forebrain and abilities of learning and memory of the rat model of Alzheimer's disease

作　　者：谷海刚[1] 龙大宏[2] 张贵平[3] 李晓滨[1] 

机构地区：[1]广州医学院组织胚胎学教研室,广州510182 [2]广州医学院解剖学教研室,广州510182 [3]广州医学院药理学教研室,广州510182

出　　处：《中国临床解剖学杂志》2009年第1期85-89,共5页Chinese Journal of Clinical Anatomy

基　　金：国家自然科学基金项目(30800345);广东省自然科学基金(06022674);广东省医学科研基金项目(B2008071);广州医学院基金项目(0706059)

摘　　要：目的:探讨神经干细胞移植对老年性痴呆模型鼠基底前脑胆碱能神经元及学习记忆能力的影响。方法:利用无血清培养技术获得新生SD鼠的基底前脑神经干细胞,切断SD大鼠左侧穹隆海马伞,基底前脑注射神经干细胞。4周后行Y迷宫测试学习记忆能力,免疫组化结合图像分析技术观察各组大鼠基底前脑胆碱能神经元变化。结果:损伤组损伤侧的内侧隔核(MS)和斜角带核(VDB)的NGFR阳性神经元大量减少,分别减少59.7%和51.4%。NSC移植组损伤侧的NGFR阳性神经元得到补充和保护,MS和VDB细胞数分别下降22.0%和26.1%。同时,NSC移植组损伤侧MS的NGFR阳性神经元的面积、周长显著增大(P<0.01),灰度显著增加(P<0.01);损伤侧VDB的NGFR阳性神经元的面积明显增大且灰度明显增加(P<0.05),周长显著增大(P<0.01)。Y迷宫测试结果显示,NSC移植组大鼠的空间学习能力得到明显改善(P<0.05),记忆能力得到显著提高(P<0.01),基底前脑NGFR阳性细胞数与大鼠的空间学习记忆能力呈正相关。结论:神经干细胞移植对老年性痴呆模型鼠基底前脑胆碱能神经元有明显的补充和保护作用,同时大鼠的学习记忆能力得到明显的改善。Objective： To study the effects of neural stem cells （NSCs） transplantation on the cholinergic neurons of the basal forebrain and abilities of learning and memory of the rat model of Alzheimer＇s disease （AD）. Methods： NSCs, obtained from basal forebrain of neonatal SD rats, were transplanted into the basal forebrain after fimbria-fornix transection. After 4 weeks, abilities of learning and memory were measured by Y-maze test. Then, the morphological changes of the cholinergic neurons in the basal forebrain were evaluated by immunohistochemistry and photo analysis. Results： NGFR-positive neurons in the medial septum （MS） and the vertical limb of the diagonal band of Broca （VDB） in lesion group decreased to 59.7% and 51.4%, comparing to that in normal group. 4 weeks after NSCs transplantation, NGFR-positive neurons in MS and VDB in NSC group was distinctly lower than that of lesion group （P〈0.01）. The area, perimeter, and gray scale of NGFR-positive neurons in MS and VDB in lesion group were significantly decreased （P〈0.05）. However, all the characteristic parameters in NSC group were significantly increased, comparing with lesion group. The ability of learning and memory in NSC group is significantly higher than that in lesion group, and almost reached to normal group. The number of NGFR-positive neurons in MS and VDB was negatively correlated with the times of learning of rats （r=-0.78-0.79, P〈0.01） and positively correlated with the ability of memory of rats （r=0.80 -0.81, P〈0.01）, which were measured by Y-maze test. Conclusions： NSCs implantation can supply and protect NGFR-positive degenerative neurons in basal forebrain and is more effective on improving the ability of spatial learning and memory in the rat model of Alzheimer＇s disease.

关 键 词：老年性痴呆 神经干细胞 胆碱能神经元 学习 记忆 大鼠 

分 类 号：R749.1[医药卫生—神经病学与精神病学]