Alteration of veratridine neurotoxicity in sympathetic neurons during development in vitro.
Neurotoxic effects of veratridine, the activator of voltage-dependent Na+ channels, were examined at various stages of in vitro development of superior cervical ganglion cells dissociated from newborn rats. Veratridine neurotoxicity did not occur in 1DIV (days in vitro) neurons, but occurred in 7DIV neurons, both of which depend on NGF for survival, but elevated K+ supports only the latter. TUNEL and electron microscopic analyses revealed that 7DIV neurons underwent both apoptotic and necrotic cell death. Veratridine was also toxic to 21DIV neurons which are independent of NGF for survival. Nuclear features of apoptosis, however, were greatly reduced in these neurons undergoing cell death, suggesting that nuclear vulnerability is also subject to developmental regulation in vitro.
Koike
T
T
Molecular Neurobiology Laboratory, Graduate School of Science, Hokkaido University, Sapporo, Japan.
Ninomiya
T
T
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000473:pathology / Q000648:ultrastructure; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D014701:Veratridine / Q000633:toxicity*
D019831:Sodium-Calcium Exchanger; D014701:Veratridine; D002118:Calcium