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Alteration of veratridine neurotoxicity in sympathetic neurons during development in vitro

Koike, T1,3; Ninomiya, T2

Neuropharmacology and Neurotoxicology

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 1 DIV (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.

1Molecular Neurobiology Laboratory, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan

2Department of Anatomy, School of Medicine, Sapporo Medical University, Sapporo 061-0800, Japan

3Corresponding Author: T. Koike

Acknowledgements: This work was partly supported by the Grant-in-Aid 64–14 for the Promotion of Fundamental Studies in Health Sciences.

Received 25 July 1999; accepted 3 November 1999

© 2000 Lippincott Williams & Wilkins, Inc.