Effects of aging and axotomy on the expression of neurotrophin receptors in primary sensory neurons

Aging is accompanied by declined sensory perception, paralleled by widespre ad dystrophic and degenerative changes in both central and peripheral senso ry pathways. Several Lines of evidence indicate that neurotrophic interacti ons are of importance for a maintained plasticity in the adult and aging ne rvous system, and that changes in the expression of neurotrophins and/or th eir receptors may underpin senile neurodegeneration. We have here examined the expression of neurotrophin receptor (p75(NTR), trkA, trkB, and trkC) mR NA and protein in intact and axotomized primary sensory neurons of young ad ult (3 months) and aged (30 months) rats. To examine possible differences a mong primary sensory neuron populations, we have studied trigeminal ganglia (TG) as well as cervical and lumbar dorsal root ganglia (DRG). In intact;a ged rats, a decrease in trk (A/B/C) mRNA labeling densities and protein-lik e immunoreactivities was observed. The decrease was most pronounced in lumb ar DRG. In contrast, a small, not statistically significant, increase of p7 5(NTR) expression was observed in aged DRG neuron profiles. After axotomy, a down-regulation of mRNA and protein levels was observed for all neurotrop hin receptors (p75(NTR), trkA, trkB and trkC) in both young adult and aged rats. Consistent with the higher expression levels of neurotrophin receptor s in unlesioned young adult primary sensory neurons, the relative effect of axotomy was more pronounced in the young adult than aged rats. Although a decrease in mean cell profile cross-sectional areas was found during aging and after axotomy, the characteristic distribution of neurotrophin receptor expression in different populations of NRG neurons was conserved. The pres ent findings suggest an attenuation of neurotrophic signaling in primary se nsory neurons with advancing age and that the expression of p75(NTR) and tr ks is regulated differently during aging. A similar dissociation of p75(NTR ) and trk regulation has previously been reported in other neuronal systems during aging, suggesting that there may be a common underlying mechanism. Decreased access to ligands, disturbed axon function and systemic changes i n androgen/estrogen levels are discussed as inducing and/or contributing fa ctors. (C) 1999 Wiley-Liss, Inc.