Downregulation of TrkA expression in primary sensory neurons after unilateral lumbar spinal nerve transection and some rescuing effects of nerve growth factor infusion.
Peripheral nerve injury results in sprouting of sympathetic and sensory nerve terminals around large diameter neurons in the dorsal root ganglia (DRG), but the underlying mechanism is not clear. Current study sought to examine changes of the nerve growth factor (NGF) receptor TrkA in DRG and spinal cord after a spinal nerve transection by an immunohistochemical technique and to investigate effects of NGF on the expression of TrkA protein in the same animal model. In the control rat, TrkA immunoreactivity was localized to about 55 +/ -1% of total neurons in DRG and to laminae I and II of the spinal cord. The percentage of TrkA immunoreactive neurons in DRG and TrkA staining intensity of spinal cord were reduced 1 week after the nerve lesion. The changes became maximal 2 weeks, but recovered partially 4 weeks after the lesion. The size of TrkA immunoreactive neurons dramatically shifted to smaller sizes, becoming more remarkable 4 weeks after the lesion. In the contralateral DRG, the percentage of TrkA immunoreactive neurons also decreased significantly. Exogenous NGF delivered to DRG for 2 weeks partially reversed the reduction of TrkA expression as well as atrophy of TrkA immunoreactive neurons. No TrkA immunoreactive basket was found around neuronal somata. Our data show that unilateral peripheral nerve injury results in dynamic downregulation of TrkA in sensory neurons in bilateral DRG and spinal cord, and that TrkA expression in sensory neurons is partially regulated by target-derived NGF.
Li
L
L
Department of Human Physiology and Centre for Neuroscience, The Flinders University of South Australia, GPO Box 2100, Adelaide 5001, Australia.
Deng
Y S
YS
Zhou
X F
XF
Yan-Shen Deng
L L
LL
D000818:Animals; D003714:Denervation; D015536:Down-Regulation; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008161:Lumbosacral Region; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000378:metabolism* / Q000473:pathology; D020671:Posterior Horn Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism*; D013127:Spinal Nerves / Q000473:pathology / Q000502:physiology*
D020932:Nerve Growth Factor; D020917:Receptor, trkA