Esmaeilzade Banafshe, Nobakht Maliheh, Joghataei Mohammad Taghi, Rahbar Roshandel Nahid, Rasouli Homa, Samadi Kuchaksaraei Ali, Hosseini Seyed Mohammad, Najafzade Nowruz, Asalgoo Sara, Hejazian Leila Beygom, Moghani Ghoroghi Fatima
Dept. of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran.
Dept. of Anatomy, School of Medicine, Bushehr University of Medical Science, Bushehr, Iran.
Iran Biomed J. 2012;16(1):1-9. doi: 10.6091/ibj.1029.2012.
Alzheimer's disease (AD) is characterized by progressive neuronal loss in hippocamp. Epidermal neural crest stem cells (EPI-NCSC) can differentiate into neurons, astrocytes and oligodendrocytes. The purpose of this study was to evaluate the effects of transplanting EPI-NCSC into AD rat model.
Two weeks after induction of AD by injection of Amyloid-β1-40 into CA1 area of rat hippocamp, Y-maze and single-trial passive avoidance tests were used to show deficit of learning and memory abilities. EPI-NCSC were obtained from the vibrissa hair follicle of rat, cultured and labeled with bromodeoxyuridine. When Alzheimer was proved by behavioral tests, EPI-NCSC was transplanted into CA3 area of hippocamp in AD rat model. The staining of EPI-NCSC markers (nestin and SOX10) was done in vitro. Double-labeling immunofluorescence was performed to study survival and differentiation of the grafted cells.
We showed that transplanted EPI-NCSC survive and produce many neurons and a few glial cells, presenting glial fibrillary acidic protein. Total number of granule cells in hippocamp was estimated to be more in the AD rat model with transplanted cells as compared to AD control group. We observed that rats with hippocampal damage made more errors than control rats on the Y-maze, when reward locations were reversed.
Transplanted cells were migrated to all areas of hippocamp and the total number of granule cell in treatment group was equal compared to control group. Transplantation of EPI-NCSC into hippocamp might differentiate into cholinergic neurons and could cure impairment of memory in AD rat model.
阿尔茨海默病(AD)的特征是海马区神经元进行性丧失。表皮神经嵴干细胞(EPI-NCSC)可分化为神经元、星形胶质细胞和少突胶质细胞。本研究的目的是评估将EPI-NCSC移植到AD大鼠模型中的效果。
通过向大鼠海马CA1区注射淀粉样β蛋白1-40诱导AD两周后,采用Y迷宫和单次试验被动回避试验来显示学习和记忆能力的缺陷。从大鼠触须毛囊中获取EPI-NCSC,进行培养并用溴脱氧尿苷标记。行为测试证实患有阿尔茨海默病后,将EPI-NCSC移植到AD大鼠模型的海马CA3区。在体外对EPI-NCSC标志物(巢蛋白和SOX10)进行染色。进行双重免疫荧光标记以研究移植细胞的存活和分化情况。
我们发现移植的EPI-NCSC存活并产生许多神经元和少量胶质细胞,呈现胶质纤维酸性蛋白。与AD对照组相比,移植细胞的AD大鼠模型海马颗粒细胞总数估计更多。我们观察到,当奖励位置颠倒时,海马受损的大鼠在Y迷宫上比对照大鼠犯更多错误。
移植的细胞迁移到海马的所有区域,治疗组颗粒细胞总数与对照组相等。将EPI-NCSC移植到海马中可能分化为胆碱能神经元,并可治愈AD大鼠模型的记忆损伤。