Differential regulation of trkA and p75 in noradrenergic pelvic autonomic ganglion cells after deafferentation of their cholinergic neighbours.
In rats, following lesion of lumbar or sacral preganglionic axons, many pelvic ganglion cells undergo axogenesis to form baskets of terminals around select populations of nearby ganglion cells. The aim of the current study was to address mechanisms underlying initiation of this sprouting, focusing on a possible role for nerve growth factor (NGF). Immunohistochemical localization of NGF receptors (trkA and p75) showed that virtually all noradrenergic and a minority of cholinergic pelvic neurons expressed both receptors. Terminals immunoreactive for each substance were found in pelvic viscera. In pelvic ganglia, many glial cells expressed p75 but not trkA, and very few lumbar or sacral preganglionic neurons expressed either receptor. Lumbar and/or sacral preganglionic inputs were removed from ganglion cells by cutting the hypogastric, pelvic or both nerves, and tissues analysed 8 days later. Levels of receptor expression in noradrenergic pelvic ganglion cells were estimated by calculating the proportion that were receptor-immunopositive, and quantifying the intensity of trkA or p75 immunofluorescence. No lesion had a significant effect on trkA expression, however, a marked decrease in p75 occurred after cutting pelvic nerves, i.e. after deafferentation of neighbouring cholinergic neurons. These injuries appeared to cause little overall change in glial p75 expression. This study shows that manipulations that trigger sprouting from noradrenergic pelvic neurons cause downregulation of p75 but not trkA. Interestingly, this is occurring while some of their target organs are synthesizing high levels of NGF. This contrasts with other NGF-sensitive cells, in which one or both receptor types are upregulated by increased exposure to the ligand. The current study is also the first to show a change in p75 expression in neurons that are neither deafferented nor axotomized.
Keast
J R
JR
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Qld 4072, Australia. j.keast@unsw.edu.au
Kepper
M E
ME
D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000737:chemistry / Q000378:metabolism*; D019771:Axotomy; D002799:Cholinergic Fibers; D005456:Fluorescent Dyes; D005725:Ganglia, Autonomic / Q000737:chemistry / Q000378:metabolism*; D007001:Hypogastric Plexus / Q000166:cytology / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D020800:Receptor, Nerve Growth Factor / Q000032:analysis / Q000378:metabolism*; D020917:Receptor, trkA / Q000032:analysis / Q000378:metabolism*; D013127:Spinal Nerves / Q000166:cytology; D013266:Stilbamidines
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D005456:Fluorescent Dyes; D020800:Receptor, Nerve Growth Factor; D013266:Stilbamidines; D020917:Receptor, trkA; D009638:Norepinephrine