Sn. Edwards et Am. Tolkovsky, CHARACTERIZATION OF APOPTOSIS IN CULTURED RAT SYMPATHETIC NEURONS AFTER NERVE GROWTH-FACTOR WITHDRAWAL, The Journal of cell biology, 124(4), 1994, pp. 537-546
Sympathetic neurons depend on nerve growth factor (NGF) for their surv
ival both in vivo and in vitro. In culture, the neurons die after NGF
withdrawal by an autonomous cell death program but whether these neuro
ns die by apoptosis is under debate. Using vital DNA stains and in sit
u nick translation, we show here that extensive chromatin condensation
and DNA fragmentation occur before plasma membrane breakdown during t
he death of NGF-deprived rat sympathetic neurons in culture. Furthermo
re, kinetic analysis of chromatin condensation events within the cell
population is consistent with a model which postulates that after NGF
deprivation nearly all of the neurons die in this manner. Although the
dying neurons display membrane blebbing, cell fragmentation into apop
totic bodies does not occur. Apoptotic events proceed rapidly at aroun
d the time neurons become committed to die, regardless of neuronal cul
ture age. However the duration of NGF deprivation required to commit n
eurons to die, and the rate at which apoptosis occurs, increase with c
ulture age. Thus, within the first week of culture, apoptosis is the p
redominant form of cell death in sympathetic neurons.