Nerve growth factor expression in parasympathetic neurons: regulation by sympathetic innervation

Interactions between sympathetic and parasympathetic nerves are important i n regulating visceral target function. Sympathetic nerves are closely appos ed to, and form functional synapses with, parasympathetic axons in many eff ector organs. The molecular mechanisms responsible for these structural and functional interactions are unknown. We explored the possibility that Nerv e Growth Factor (NGF) synthesis by parasympathetic neurons provides a mecha nism by which sympathetic-parasympathetic interactions are established. Par asympathetic pterygopalatine ganglia NGF-gene expression was examined by in situ hybridization and protein content assessed by immunohistochemistry. U nder control conditions, NGF mRNA was present in approximate to 60% and NGF protein was in 40% of pterygopalatine parasympathetic neurons. Peripheral parasympathetic axons identified by vesicular acetylcholine transporter-imm unoreactivity also displayed NGF immunoreactivity. To determine if sympathe tic innervation regulates parasympathetic NGF expression, the ipsilateral s uperior cervical ganglion was excised. Thirty days postsympathectomy, the n umbers of NGF mRNA-positive neurons were decreased to 38% and NGF immunorea ctive neurons to 15%. This reduction was due to a loss of sympathetic nerve impulse activity, as similar reductions were achieved when superior cervic al ganglia were deprived of preganglionic afferent input for 40 days. These findings provide evidence that normally NGF is synthesized by parasympathe tic neurons and transported anterogradely to fibre terminals, where it may be available to sympathetic axons. Parasympathetic NGF expression, in turn, is augmented by impulse activity within (and presumably transmitter releas e from) sympathetic axons. It is suggested that parasympathetic NGF synthes is and its modulation by sympathetic innervation provides a molecular basis for establishment and maintenance of autonomic axo-axonal synaptic interac tions.