Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory neurons of aged mice.
Sensory neurons in aging mammals undergo changes in anatomy, physiology and gene expression that correlate with reduced sensory perception. In this study we compared young and aged mice to identify proteins that might contribute to this loss of sensation. We first show using behavioral testing that thermal sensitivity in aged male and female mice is reduced. Expression of sodium channel (Nav1.8 and Nav1.9) and transient receptor potential vanilloid (TRPV) channels in DRG and peripheral nerves of young and old male mice was then examined. Immunoblotting and RT-PCR assays showed reduced Nav1.8 levels in aged mice. No change was measured in TRPV1 mRNA levels in DRG though TRPV1 protein appeared reduced in the DRG and peripheral nerves. The GFRalpha3 receptor, which binds the growth factor artemin and is expressed by TRPV1-positive neurons, was also decreased in the DRG of aged animals. These findings indicate that loss of thermal sensitivity in aging animals may result from a decreased level of TRPV1 and Nav1.8 and decreased trophic support that inhibits efficient transport of channel proteins to peripheral afferents.
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Shuying
S
Wang
Brian M
BM
Davis
Melissa
M
Zwick
Stephen G
SG
Waxman
Kathryn M
KM
Albers
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D015870:Gene Expression / Q000502:physiology*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009412:Nerve Fibers / Q000378:metabolism; D009475:Neurons, Afferent / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011930:Reaction Time / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012737:Sex Factors; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D013697:Thermosensing / Q000502:physiology*
C494994:Gfra3 protein, mouse; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D062559:NAV1.8 Voltage-Gated Sodium Channel; D012333:RNA, Messenger; C568318:Scn10a protein, mouse; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse