Alzheimer Disease ; therapy ; Animals ; Cell Differentiation ; Embryo, Mammalian ; cytology ; Male ; Maze Learning ; Mice ; Mice, Inbred C57BL ; Parasympathetic Nervous System ; cytology ; Stem Cell Transplantation

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.

Objective To elucidate the differentiation of embryonic stem cells (ESCs) after their transplantation into mouse models of Alzheimer's disease (AD), and observe the changes of learning and memory abilities of the mice. Methods The C57BL/6 AD mice were randomly divided into 4 groups:dementia group (n=14), enjoying the dementia in the mouse models of right nucleus basalis of Meynert (NBM) lesion destroyed by Ibotenic; sham-operated group (n=14), injecting PBS in the right NBM;transplantation group (n=12), enjoying the dementia in the mouse models of right NBM lesion destroyed by Ibotenic and performing transplantation with ESCs in the frontal and parietal cortices; and normal control group (n=12), without giving any treatment. Behavioral tests by eight-arm radial maze were conducted to evaluate the changes of learning and memory abilities of the mice 12 weeks after the transplantation. HE staining and double staining of HuC/D-green fluorescent protein (GFP) and glial fibrillary acid protein (GFAP)-GFP were performed to observe the differentiation of ESCs in the cortices 12 weeks after their transplantation. Results It was demonstrated by HE staining that the ESCs transplanted into the cortices developed into malignant teratoma in all AD mice and the frontal lobe had the largest one;no expressions of HuC/D and GFPA were noted. The value of working memory error (WME) in mice of the dementia group was significantly higher than that in the normal controls (t=6.130,P=0.000), while the WME value in the mice of transplantation group was obviously higher than that in the mice of dementia group (t=6.460, P=0.000). The value of reference memory error between each 2 groups was not significantly different (F=0.144, P=0.065). Conclusion ESCs transplanted into the frontal and parietal cortices cannot be differentiated into neurons or glias but into tetratoma, and recent memory disruption of AD mice even worsen.