Effects of systemically administered NT‐3 on sensory neuron loss and nestin expression following axotomy

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Abstract
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 μm and expressed the neuronal markers neurofilament 200, βIII‐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. J. Comp. Neurol. 482:320–332, 2005.