Rescue of adult mouse motoneurons from injury-induced cell death by glial cell line-derived neurotrophic factor.
Glial cell line-derived neurotrophic factor (GDNF) has been shown to rescue developing motoneurons in vivo and in vitro from both naturally occurring and axotomy-induced cell death. To test whether GDNF has trophic effects on adult motoneurons, we used a mouse model of injury-induced adult motoneuron degeneration. Injuring adult motoneuron axons at the exit point of the nerve from the spinal cord (avulsion) resulted in a 70% loss of motoneurons by 3 weeks following surgery and a complete loss by 6 weeks. Half of the loss was prevented by GDNF treatment. GDNF also induced an increase (hypertrophy) in the size of surviving motoneurons. These data provide strong evidence that the survival of injured adult mammalian motoneurons can be promoted by a known neurotrophic factor, suggesting the potential use of GDNF in therapeutic approaches to adult-onset motoneuron diseases such as amyotrophic lateral sclerosis.
Li
L
L
Department of Neurobiology and Anatomy, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
Wu
W
W
Lin
L F
LF
Lei
M
M
Oppenheim
R W
RW
Houenou
L J
LJ
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D002452:Cell Count; D002460:Cell Line; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006651:Histocytochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009252:NADPH Dehydrogenase / Q000302:isolation & purification; D009410:Nerve Degeneration / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D013126:Spinal Nerve Roots / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000601:surgery
D019208:Brain-Derived Neurotrophic Factor; C495040:Gdnf protein, mouse; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase