Protective effect of HSV-mediated gene transfer of nerve growth factor in pyridoxine neuropathy demonstrates functional activity of trkA receptors in large sensory neurons of adult animals.
The distinct distribution of trkA receptors on small neurons and trkC receptors on large neurons in the dorsal root ganglion correlates with the dependence of these two classes of neurons on nerve growth factor and neurotrophin-3, respectively, for survival during development. In adult animals, the distribution of high affinity neurotrophin (trk) is complex and overlapping; neurotrophins are not required for cell survival, but may influence cell phenotype and the response to injury. In order to test the functional activity of trkA receptors in the sensory ganglia of adult animals in vivo, we examined the ability of a nerve growth factor-expressing recombinant replication-defective herpes simplex virus-based vector to prevent the selective degeneration of large sensory fibres caused by intoxication with pyridoxine. Transduction of dorsal root ganglion neurons in vivo by subcutaneous inoculation of the nerve growth factor-expressing vector prevented the development of pyridoxine-induced neuropathy measured by electrophysiological, morphological and behavioural measures. These results demonstrate a functional activity of trkA receptors expressed on large neurons in the dorsal root ganglion in mature animals; this observation has important implications for the choice of neurotrophic factors for treatment of peripheral nerve disease.
Chattopadhyay
Munmun
M
Department of Neurology, University of Pittsburgh, USA.
Goss
James
J
Lacomis
David
D
Goins
William C
WC
Glorioso
Joseph C
JC
Mata
Marina
M
Fink
David J
DJ
D000818:Animals; D001522:Behavior, Animal; D002470:Cell Survival; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005071:Evoked Potentials; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism / Q000821:virology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D009414:Nerve Growth Factors / Q000378:metabolism; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D011247:Pregnancy; D011736:Pyridoxine; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D020426:Sciatic Neuropathy / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D018139:Simplexvirus / Q000235:genetics*
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D011736:Pyridoxine