Transplantation of cholinergic neural stem cells in a mouse model of Alzheimer's disease
10.3760/cma.j.issn.1671-8925.2008.12.005
- VernacularTitle:胆碱能神经干细胞在阿尔茨海默病小鼠的移植研究
- Author:
Qing-Hua WANG
1
;
Ru-Xiang XU
;
Seigo NAGAO
Author Information
1. 南方医科大学珠江医院
- Keywords:
Neural stem cells;
Alzheimer's disease;
Acetylcholine
- From:
Chinese Journal of Neuromedicine
2008;7(12):1204-1208
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the therapeutic effect of cholinergic neural stem cell (NSC) transplantation in a mouse model of Alzheimer's disease (AD). Methods Ibotenic acid was injected into the nucleus basalis ofMeynert (NBM) of C57BL/6 mice to establish a mouse model of AD. Four weeks after the injection, mouse embryonic stem cell (ES)-derived cholinergic NSCs were transplanted into the frontal and the barrel field of the S1 cortex. Behavioral tests using eight-arm radial maze were conducted 8 weeks after the transplantation, and the survival and differentiation of the transplanted NSCs were evaluated with double staining of choline acetyltransferase (CHAT), serotonin, amyloid-a protein (Aa) and green fluorecent protein (GFP) 12 weeks after transplantation. Results The cholinergic NSCs transplanted into mouse cortices survived and produced a large number of adult ChAT-positive neurons and a small amount of serononin-positive neurons in and around the grafts. The expression of Aain the surrounding cortex was significantly reduced, and the working memory error significantly decreased in mice grafted with cholinergic NSCs. Conclusion Transplantation of cholinergic NSCs into the prefrontal and parietal cortices can partially reconstruct the cholinergic innervation and significantly improve recent memory disruption in mice with NBM damage.