Transplantation of mouse embryonic stem cell-derived neurons into the striatum, subthalamic nucleus and substantia nigra, and behavioral recovery in hemiparkinsonian rats.
Usefulness of the in vitro and in vivo generation of neural precursors from embryonic stem (ES) cells has been widely discussed, but functional recovery in animal models of Parkinson's disease (PD) is not fully understood. The aim of this study was to investigate a transplantation strategy for PD by assessing whether double-transplants in the striatum (ST) and substantia nigra (SN), or ST and subthalamic nucleus (STN) induce functional recovery in 6-hydroxydopamine-lesioned rats. Methamphetamine-induced rotation was significantly reduced by transplantation of mouse ES cell-derived neurons into the ST, but not the STN or SN alone. Double-transplantation was also effective at recovering rotational behavior. Although immunoreactivity for tyrosine hydroxylase (TH) was almost completely lost in the ipsilateral striatum in hemiparkinsonian rats, TH immunoreactivity was detected in transplanted cells and sprouting fibers in the ST, STN and SN. These results suggest that both the involvement of ST as a place of transplantation and the number of ES cell-derived neurons are essential factors for efficacy on hemiparkinsonian behaviors.
Inden
Masatoshi
M
Department of Neurobiology, 21st Century COE Program, Kyoto Pharmaceutical University, Misasagi Yamashina-ku, Kyoto 607-8414, Japan.
Kim
Do-hoon
DH
Qi
Meirigeng
M
Kitamura
Yoshihisa
Y
Yanagisawa
Daijiro
D
Nishimura
Kaneyasu
K
Tsuchiya
Daiju
D
Takata
Kazuyuki
K
Hayashi
Kousuke
K
Taniguchi
Takashi
T
Yoshimoto
Kanji
K
Shimohama
Shun
S
Sumi
Shoichiro
S
Inoue
Kazutomo
K
D000818:Animals; D001479:Basal Ganglia / Q000503:physiopathology / Q000601:surgery*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D016380:Brain Tissue Transplantation / Q000379:methods*; D002452:Cell Count; D003342:Corpus Striatum / Q000503:physiopathology / Q000601:surgery; D003714:Denervation; D004195:Disease Models, Animal; D006085:Graft Survival / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism; D006948:Hyperkinesis / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000637:transplantation*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000503:physiopathology / Q000628:therapy*; D039904:Pluripotent Stem Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D013378:Substantia Nigra / Q000503:physiopathology / Q000601:surgery; D020531:Subthalamic Nucleus / Q000503:physiopathology / Q000601:surgery
D008694:Methamphetamine; D016627:Oxidopamine