GDNF and BDNF alter the expression of neuronal NOS, c-Jun, and p75 and prevent motoneuron death following spinal root avulsion in adult rats

J Neurotrauma. 2003 Jun;20(6):603-12. doi: 10.1089/089771503767168528.

Abstract

In the present study, we examined the effects of glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and insulin growth factor (IGF-1) on adult motoneuron survival following spinal root avulsion. The expression of neuronal nitric oxide synthase (nNOS), c-Jun, and the low-affinity neurotrophin receptor (P75) following treatment with these neurotrophic factors was also examined. In control animals, approximately 80% of spinal motoneurons were nNOS positive at 3 weeks following the lesion, whereas in GDNF or BDNF treated animals no nNOS positive motoneurons were found at the same time point. Following injury and treatment with GDNF and BDNF increased numbers of motoneurons were c-Jun and P75 positive. By 6 weeks following the lesion, only approximately 28% of motoneurons persisted in control animals whereas about 90% of motoneurons survived injury following treatment with either GDNF or BDNF. In contrast, CNTF and IGF-1 were ineffective in either inhibiting nNOS expression or preventing motoneuron death. Our results provide in vivo evidence that the survival of injured adult mammalian motoneurons can be promoted by specific neurotrophic factors, and that this effect is associated with inhibition of nNOS expression and up-regulation of c-Jun and P75 expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Brain-Derived Neurotrophic Factor / therapeutic use
  • Cell Death / drug effects
  • Cell Death / physiology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Glial Cell Line-Derived Neurotrophic Factor
  • Male
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Nerve Growth Factors / pharmacology*
  • Nerve Growth Factors / therapeutic use
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase Type I
  • Proto-Oncogene Proteins c-jun / biosynthesis*
  • Proto-Oncogene Proteins c-jun / genetics
  • Radiculopathy / drug therapy
  • Radiculopathy / metabolism*
  • Radiculopathy / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor / biosynthesis*
  • Receptors, Nerve Growth Factor / genetics

Substances

  • Brain-Derived Neurotrophic Factor
  • Gdnf protein, rat
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Proto-Oncogene Proteins c-jun
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nos1 protein, rat