title: Pharmacological characteristics of rotational behavior in hemiparkinsonian rats transplanted with mouse embryonic stem cell-derived neurons.
abstract: Embryonic stem (ES) cells have many of the characteristics of an optimal cell source for cell-replacement therapy. Although the usefulness of the in vitro generation of dopamine (DA)-neural precursors from ES cells has been widely discussed, functional recovery in animal models of Parkinson's disease is not fully understood. In 6-hydroxydopamine-lesioned rats, apomorphine markedly induced contralateral rotation. Apomorphine-induced rotation was significantly reduced by transplantation of neuron-like cells that had differentiated from mouse ES cells using nicotinamide, but not L-lysine. In addition, methamphetamine-induced ipsilateral rotation was significantly reduced. On the other hand, picrotoxin did not inhibit apomorphine-induced rotational asymmetry. Fluoxetine alone and fenfluramine alone induced slight contralateral rotation and rotation in both directions, respectively, and these effects were similar in transplanted rats. 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 contrast, immunoreactivities for gamma-aminobutyric acid (GABA) and serotonin (5-HT) neurons were not changed. These results suggest that improvement of rotational behavior may be induced predominantly by transplantation of nicotinamide-treated ES cell-derived DA neurons, rather than by changes in the activities of GABA or 5-HT neural systems, in hemiparkinsonian rats.
authors.affiliation: Department of Neurobiology, Kyoto Pharmaceutical University, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inden
authors.forename: Dohoon
authors.initials: D
authors.lastname: Kim
authors.forename: Yuanjin
authors.initials: Y
authors.lastname: Gu
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kondo
authors.forename: Daiju
authors.initials: D
authors.lastname: Tsuchiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
authors.forename: Akinori
authors.initials: A
authors.lastname: Akaike
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Sumi
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Inoue
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000637:transplantation*; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology; D013378:Substantia Nigra / Q000166:cytology / Q000637:transplantation