Ag. Estevez et al., NITRIC OXIDE-DEPENDENT PRODUCTION OF CGMP SUPPORTS THE SURVIVAL OF RAT EMBRYONIC MOTOR-NEURONS CULTURED WITH BRAIN-DERIVED NEUROTROPHIC FACTOR, The Journal of neuroscience, 18(10), 1998, pp. 3708-3714
Trophic factor deprivation induces neuronal nitric oxide synthase (NOS
) and apoptosis of rat embryonic motor neurons in culture. We report h
ere that motorneurons constitutively express endothelial NOS that help
s support the survival of motor neurons cultured with brain-derived ne
urotrophic factor (BDNF) by activating the nitric oxide-dependent solu
ble guanylate cyclase. Exposure of BDNF-treated motor neurons to nitro
-L-arginine methyl ester (L-NAME) decreased cell survival 40-50% 24 hr
after plating. Both low steady-state concentrations of exogenous nitr
ic oxide (<0.1 mu M) and cGMP analogs protected BDNT-treated motor neu
rons from death induced by L-NAME. Equivalent concentrations of cAMP a
nalogs did not affect cell survival. Inhibition of nitric oxide-sensit
ive guanylate cyclase with 2 mu M 1H-[1,2,4]oxadiazolo[4,3-a]quinoxali
n-1-one (ODQ) reduced the survival of BDNF-treated motor neurons by 35
%. cGMP analogs also protected from ODQ-induced motor neuron death, wh
ereas exogenous nitric oxide did not. In all cases, cell death was pre
vented with caspase inhibitors. Our results suggest that nitric oxide-
stimulated cGMP synthesis helps to prevent apoptosis in BDNF-treated m
otor neurons.