Neuronal survival during electrical blockade is increased by 8-bromo cyclic adenosine 3',5' monophosphate

Dissociated cultures from spinal cord-dorsal root ganglion were used as a model system to study the interaction between electrical activity and cyclic nucleotides on neuronal survival. Neuronal death produced by electrical blockade with tetrodotoxin (TTX) was attenuated by the addition of 8-Bromo cyclic AMP (8-Br cAMP). [125I]Tetanus toxin fixation, choline acetyltransferase activity and neuronal cell counts were used to quantitate the effects of 8-Br cAMP on the cultures. A dose-dependent increase in both tetanus toxin fixation (neuronal surface marker) and choline acetyltransferase activity was observed with 8-Br cAMP application to TTX-treated cultures as compared to those treated with TTX alone. The rate of choline acetyltransferase induction by 8-Br cAMP was decreased in the presence of TTX. Supplementation of the cultures with 8-bromo cyclic GMP, under the same conditions, had no protective or inductive effects. These data suggest that cholinergic neurons are among those cells affected by electrical blockade and by increased culture cAMP levels. Electrical blockade with TTX produced significant decreases in cAMP levels during a critical period in development. The onset of the critical period was found to be between day 5 and day 8 in vitro and the vulnerability to TTX-mediated decreases in cAMP were not evident in cultures which were older than 1 month. Conditioned medium obtained from spinal cord-dorsal root ganglion cultures before the critical period were tested on TTX-treated cultures that were within the critical period. No decrease in cAMP levels from that of controls was observed after 50% conditioned medium plus TTX treatment.(ABSTRACT TRUNCATED AT 250 WORDS)