PMID- 12906744 OWN - NLM STAT- MEDLINE DCOM- 20030916 LR - 20071114 IS - 0897-7151 (Print) IS - 0897-7151 (Linking) VI - 20 IP - 6 DP - 2003 Jun TI - GDNF and BDNF alter the expression of neuronal NOS, c-Jun, and p75 and prevent motoneuron death following spinal root avulsion in adult rats. PG - 603-12 AB - 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. FAU - Wu, Wutian AU - Wu W AD - Department of Anatomy, Faculty of Medicine, University of Hong Kong, Hong Kong, China. wtwu@hkucc.hku.hk FAU - Li, Linxi AU - Li L FAU - Yick, Leung-Wah AU - Yick LW FAU - Chai, Hong AU - Chai H FAU - Xie, Yuanyun AU - Xie Y FAU - Yang, Yi AU - Yang Y FAU - Prevette, David M AU - Prevette DM FAU - Oppenheim, Ronald W AU - Oppenheim RW LA - eng GR - NS 20402/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurotrauma JT - Journal of neurotrauma JID - 8811626 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Gdnf protein, rat) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (Receptor, Nerve Growth Factor) RN - 0 (Receptors, Nerve Growth Factor) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type I) RN - EC 1.14.13.39 (Nos1 protein, rat) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology/therapeutic use MH - Cell Death/drug effects/physiology MH - Gene Expression Regulation/drug effects/physiology MH - Glial Cell Line-Derived Neurotrophic Factor MH - Male MH - Motor Neurons/drug effects/metabolism/pathology MH - Nerve Growth Factors/*pharmacology/therapeutic use MH - Nitric Oxide Synthase/*biosynthesis/genetics MH - Nitric Oxide Synthase Type I MH - Proto-Oncogene Proteins c-jun/*biosynthesis/genetics MH - Radiculopathy/drug therapy/*metabolism/pathology MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, Nerve Growth Factor MH - Receptors, Nerve Growth Factor/*biosynthesis/genetics EDAT- 2003/08/09 05:00 MHDA- 2003/09/17 05:00 CRDT- 2003/08/09 05:00 PHST- 2003/08/09 05:00 [pubmed] PHST- 2003/09/17 05:00 [medline] PHST- 2003/08/09 05:00 [entrez] AID - 10.1089/089771503767168528 [doi] PST - ppublish SO - J Neurotrauma. 2003 Jun;20(6):603-12. doi: 10.1089/089771503767168528.