Abstract
Because damage to sympathetic nerve terminals occurs in a variety of diseases, we tested the hypothesis that nerve terminal damage per se is sufficient to impair ganglionic neurotransmission in vivo. First, we measured the effect of nerve terminal damage produced by the sympathetic nerve terminal toxin 6-hydroxydopamine (6-OHDA) on ganglionic levels of several neurotrophins thought to promote neurotransmission. 6-OHDA-induced nerve terminal damage did not decrease the expression of neurotrophin-4 or brain-derived neurotrophic factor mRNA in the celiac ganglia but did decrease the ganglionic content of both nerve growth factor protein (nadir = -63%) and the mRNA of the alpha-3 subunit of the nicotinic cholinergic receptor (nadir = -49%), a subunit required for neurotransmission. Next, we tested whether this degree of receptor deficiency was sufficient to impair activation of celiac ganglia neurons. Impaired fos mRNA responses to nicotine administration in the celiac ganglia of 6-OHDA-pretreated rats correlated temporally with suppressed expression of functional nicotinic receptors. We verified by Fos protein immunohistochemistry that this ganglionic impairment was specific to principal ganglionic neurons. Last, we tested whether centrally initiated ganglionic neurotransmission is also impaired following nerve terminal damage. The principal neurons in rat celiac ganglia were reflexively activated by 2-deoxy-glucose-induced glucopenia, and the Fos response in the celiac ganglia was markedly inhibited by pretreatment with 6-OHDA. We conclude that sympathetic nerve terminal damage per se is sufficient to impair ganglionic neurotransmission in vivo and that decreased nicotinic receptor production is a likely mediator.