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

• Published in: Journal of comparative neurology (1911) 1999-08, Vol.410 (3), p.368-386
• Main Authors: Bergman, E., Fundin, B.T., Ulfhake, B.
• Format: Article
• Language: English
• Subjects: Aging - physiology; Animals; Axotomy; behavior; Female; Ganglia, Spinal - growth & development; Ganglia, Spinal - metabolism; Gene Expression Regulation; Gene Expression Regulation, Developmental; immunohistochemistry; in situ hybridization; Neurons, Afferent - physiology; neurotrophins; Proto-Oncogene Proteins - genetics; Rats; Rats, Sprague-Dawley; Receptor Protein-Tyrosine Kinases - genetics; Receptor, Ciliary Neurotrophic Factor; Receptor, Nerve Growth Factor; Receptor, trkA; Receptor, trkC; Receptors, Nerve Growth Factor - genetics; RNA, Messenger - genetics; Transcription, Genetic; Trigeminal Ganglion - growth & development; Trigeminal Ganglion - metabolism
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/(SICI)1096-9861(19990802)410:3<368::AID-CNE2>3.0.CO;2-I

Aging is accompanied by declined sensory perception, paralleled by widespread dystrophic and degenerative changes in both central and peripheral sensory pathways. Several lines of evidence indicate that neurotrophic interactions are of importance for a maintained plasticity in the adult and aging nervous system, and that changes in the expression of neuro‐trophins and/or their receptors may underpin senile neurodegeneration. We have here examined the expression of neurotrophin receptor (p75NTR, trkA, trkB, and trkC) mRNA and protein in intact and axotomized primary sensory neurons of young adult (3 months) and aged (30 months) rats. To examine possible differences among primary sensory neuron populations, we have studied trigeminal ganglia (TG) as well as cervical and lumbar dorsal root ganglia (DRG). In intact aged rats, a decrease in trk (A/B/C) mRNA labeling densities and protein‐like immuno‐reactivities was observed. The decrease was most pronounced in lumbar DRG. In contrast, a small, not statistically significant, increase of p75NTR expression was observed in aged DRG neuron profiles. After axotomy, a down‐regulation of mRNA and protein levels was observed for all neurotrophin receptors (p75NTR, trkA, trkB and trkC) in both young adult and aged rats. Consistent with the higher expression levels of neurotrophin receptors 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 present findings suggest an attenuation of neurotrophic signaling in primary sensory neurons with advancing age and that the expression of p75NTR and trks is regulated differently during aging. A similar dissociation of p75NTR 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 in androgen/estrogen levels are discussed as inducing and/or contributing factors. J. Comp. Neurol. 410:368–386, 1999. © 1999 Wiley‐Liss, Inc.