CYCLIC-AMP AND SYMPATHETIC NEURONAL PROGRAMMED CELL-DEATH

The survival and proper functioning of sympathetic neurons are depende nt on nerve growth factor (NGF). When immature sympathetic neurons are deprived of NGF, they undergo an 'active' dying process usually terme d 'programmed cell death' or 'apoptosis'. This trophic factor dependen ce is age related such that the cells become less dependent on NGF as they mature. Removal of NGF in immature cultures, which triggered the process of programmed eel: death, resulted in a significant decrease o f intracellular cAMP levels. In contrast, when these cells matured in culture and became relatively NGF independent, NGF withdrawal did nor lead to a drop of cAMP levels. Pituitary adenylate cyclase-activating polypeptide (PACAP), a naturally occurring bioactive peptide structura lly similar to VIP, could increase cAMP levels in these sympathetic ne urons, and delay neuronal cell death resulting from NGF deprivation. T hese results suggest that PACAP may serve as a neurotrophic factor in sympathetic neurons. (C) 1997 Elsevier Science Ltd.