Neuropeptides and neurotrophin receptor mRNAs in primary sensory neurons of aged rats.
Neuropeptides and neurotrophin receptors are regulated in primary sensory neurons in response to axonal injury, and axonal lesions are characteristic stigmata of aging primary sensory neurons. We have therefore examined the expression of neuropeptides and neurotrophin receptor mRNAs in 30-month-old (median survival age) Sprague-Dawley rats to see if similar adaptive mechanisms operate in senescence. The content of neuropeptides was examined with immunohistochemistry (IHC) and in situ hybridization (ISH), and the cellular mRNA expression of neurotrophin receptors was studied with ISH. All of the aged rats had symptoms of hind limb incapacity (posterior paralysis), but fore limbs did not seem affected. The size-distribution of neuronal profiles in cervical and lumbar dorsal root ganglia (DRGs) was similar in aged and young adult (2-3 months old) rats. In aged rats, the DRG neurons showed an increase in both immunolabelling and mRNA content of neuropeptide tyrosine (NPY), as well as an increased cellular expression of galanin mRNA. In the same animals, there were decreased cellular levels of calcitonin gene-related peptide (CGRP; IHC and ISH) and substance P (SP; IHC and ISH), while the difference in neuronal somatostatin (IHC and ISH) was small. The distribution of neuropeptide immunoreactivities in the dorsal horn of the corresponding spinal cord segments revealed a decreased labelling for CGRP-, SP-, and somatostatin-like immunoreactivities (LI) in the aged rats at both cervical and lumbar levels. NPY- and galanin-LI had a similar distribution in aged and young adult rats. NPY-immunoreactive fibers were also encountered in the dorsal column of aged but not young adult rats. ISH revealed that most of the primary sensory neurons express mRNA for the p75 low-affinity neurotrophin receptor (p75-LANR) and that there was no discernible difference between young adult and aged rats. The labelling intensity for mRNA encoding high-affinity tyrosine kinase receptors (TrkA, TrkB, and TrkC) was decreased in aged rat DRG neurons, while the percentage of neuronal profiles expressing mRNA for TrkA/B/C was similar in young adult and aged rats. The changed pattern of neuropeptide expression in primary sensory neurons of aged rats resembled that seen in young adult rats subjected to axonal injury of peripheral sensory nerves and may, thus, indicate aging-related lesions of sensory fibers. Since NPY is primarily present in large and galanin in small DRG neurons, the stronger effect on NPY as compared to galanin expression may indicate that aging preferentially affects neurons associated with mechanoreception (A alpha and A beta fibers) as compared to nociceptive units (A delta and C fibers). Furthermore, the observed changes in neuropeptide expression were most pronounced in lumbar DRGs, that harbors the sensory neurons supplying the affected hindlimbs of the rats.
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
E
E
Bergman
H
H
Johnson
X
X
Zhang
T
T
Hökfelt
B
B
Ulfhake
D000222:Adaptation, Physiological; D000375:Aging / Q000378:metabolism*; D000818:Animals; D005727:Ganglia, Spinal / Q000737:chemistry* / Q000166:cytology; D017403:In Situ Hybridization; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D009475:Neurons, Afferent / Q000737:chemistry*; D009478:Neuropeptide Y / Q000032:analysis; D009479:Neuropeptides / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D020801:Receptor, Ciliary Neurotrophic Factor; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000032:analysis; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000235:genetics*
D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020812:Receptor, trkC