Neural stem cells transplantation in cortex in a mouse model of Alzheimer's disease.
OBJECTIVE
The goal of this study was to elucidate the effect of neurospheres (NS) on dementia in the mouse model of nucleus basalis of Meynert (NBM) lesion.


METHODS
Mouse embryonic stem cell (ES) derived neurospheres were transplanted into the frontal association cortex and barrel field of S1 cortex of C57BL/6 mice 4 weeks after including a lesion of NBM by ibotenic acid, while other healthy mice that received ES cells served as control. Behavioral tests by 8-arm radial maze were conducted 8 weeks after transplantation, and double staining of choline acetyltransferase (ChAT), serotonin, amyloid-beta protein (AP) and green fluorescent protein (GFP) 12 weeks after transplantation. We found that the neurospheres transplanted into the mouse cortex survived and produced many ChAT-positive neurons and a few serotonin-positive neurons in and around the grafts. The working memory error decreased significantly in the mice grafted with neurospheres. In contrast, the ES cells developed into teratomas in all of the control mice and expressed no neurons, and the working memory deteriorated remarkably.


CONCLUSIONS
Transplantation of neurospheres, but not ES cells, into the prefrontal and parietal cortices, dramatically alleviated the cholinergic deficits and recent memory disruption in the NBM lesioned mice.
Department of Neurological Surgery, Faculty of Medicine, Kagawa University, Kita-gun, Japan.
Qinghua
Q
Wang
Yoshihito
Y
Matsumoto
Tokuhisa
T
Shindo
Keisuke
K
Miyake
Atsushi
A
Shindo
Masahiko
M
Kawanishi
Nobuyuki
N
Kawai
Takashi
T
Tamiya
Seigo
S
Nagao
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000637:transplantation*; D033581:Stem Cell Transplantation