Dopamine induces apoptosis-like cell death in cultured chick sympathetic neurons--a possible novel pathogenetic mechanism in Parkinson's disease.
We report that exposure of cultured, postmitotic chick-embryo sympathetic neurons, to physiological concentrations of dopamine (0.1-1 mM) for 24 h initiates a cellular death process characteristic of apoptosis (= programmed-cell-death, PCD). Dopamine caused marked morphological alterations, mainly axonal disintegration and severe shrinkage and condensation of cell bodies. Flow-cytometric analysis of propidium-iodide-stained cell nuclei revealed the characteristic apoptotic nuclear fragmentation: increase in nuclear granularity and emergence of a large, distinct population of nuclei with reduced DNA content (subdiploid, apoptotic peak). These alterations were similar to changes induced by nerve growth factor (NGF) deprivation, a model of sympathetic neuronal PCD. Alterations were inhibited by the anti-oxidative agent DTT. Inappropriate, dopamine-induced activation of PCD might have a role in nigral neuronal degeneration in Parkinson's disease.
Ziv
I
I
Department of Neurology, Beilinson Medical Center, Petah-Tiqva, Israel.
Melamed
E
E
Nardi
N
N
Luria
D
D
Achiron
A
A
Offen
D
D
Barzilai
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D002642:Chick Embryo; D004396:Coloring Agents; D004249:DNA Damage; D004298:Dopamine / Q000494:pharmacology*; D005434:Flow Cytometry; D009474:Neurons / Q000187:drug effects*; D010300:Parkinson Disease / Q000473:pathology*; D013564:Sympathetic Nervous System / Q000166:cytology* / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles
D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D004298:Dopamine