Inhibition by rotenone of mesencephalic neural stem-cell migration in a neurosphere assay in vitro.
Parkinson disease is an age-related neurodegenerative disorder. Although the underlying pathophysiological mechanisms are incompletely understood, it has been suggested that environmental origins of sporadic Parkinson disease occur early in life. Here we examined the in vitro effects of the environmental dopaminergic toxin rotenone on neural stem cells, derived from the rat E16 mesencephalon. The neurospheres were cultured on the uncoated glass dishes. Cells emerged from the neurospheres and migrated along the radial axis. The migrating populations comprised cells that were positive for nestin, microtubule-associated proteins, and glial fibrillary acidic protein. Exposure to rotenone inhibited cell migration, decreased proliferative cells in a dose-dependent manner, and increased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells. Quantitative analysis revealed a linear function between the inhibition of migration and the rotenone concentration. Thus, we showed for the first time that rotenone exerted inhibitory effects on the migration as well as the proliferation of neural stem cells in vitro.
Ishido
Masami
M
Environmental Risk Research Program, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan. ishidou@nies.go.jp
Suzuki
Junko
J
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D007306:Insecticides / Q000633:toxicity*; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D012402:Rotenone / Q000633:toxicity*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology
D007306:Insecticides; D019394:Ki-67 Antigen; D012402:Rotenone