Effects of systemically administered NT-3 on sensory neuron loss and nestin expression following axotomy.
Previous work has shown that administration of the neurotrophin NT-3 intrathecally or to the proximal stump can prevent axotomy-induced sensory neuron loss and that NT-3 can stimulate sensory neuron differentiation in vitro. We have examined the effect of axotomy and systemic NT-3 administration on neuronal loss, apoptosis (defined by morphology and activated caspase-3 immunoreactivity), and nestin expression (a protein expressed by neuronal precursor cells) in dorsal root ganglia (DRG) following axotomy of the adult rat sciatic nerve. Systemic administration of 1.25 or 5 mg of NT-3 over 1 month had no effect on the incidence of apoptotic neurons but prevented the overall loss of neurons seen at 4 weeks in vehicle-treated animals. Nestin-immunoreactive neurons began to appear 2 weeks after sciatic transection in untreated animals and steadily increased in incidence over the next 6 weeks. NT-3 administration increased the number of nestin-immunoreactive neurons at 1 month by two- to threefold. Nestin-IR neurons had a mean diameter of 20.78 +/- 2.5 microm and expressed the neuronal markers neurofilament 200, betaIII-tubulin, protein gene product 9.5, growth associated protein 43, trkA, and calcitonin gene-related peptide. Our results suggest that the presence of nestin in DRG neurons after nerve injury is due to recent differentiation and that exogenous NT-3 may prevent neuron loss by stimulating this process, rather than preventing neuron death.
Kuo
Lu-Ting
LT
Department of Molecular Neuroscience, Division of Neuropathology, Institute of Neurology, London WC1N 3BG, UK.
Simpson
Andrew
A
Schänzer
Anne
A
Tse
Jamie
J
An
Shu-Feng
SF
Scaravilli
Francesco
F
Groves
Michael J
MJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019771:Axotomy; D015415:Biomarkers; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D048429:Cell Size; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D015918:Infusion Pumps, Implantable; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D064231:Nestin; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D020933:Neurotrophin 3 / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D015415:Biomarkers; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases