Leukemia inhibitory factor prevents the death of axotomised sensory neurons in the dorsal root ganglia of the neonatal rat.
Leukemia inhibitory factor (LIF) has several characteristics of a neurotrophic factor for sensory neurons. Here we have investigated whether LIF also supports the survival of axotomised sensory neurons in vivo. Newborn rat pups received a unilateral sciatic nerve transection and the injury site was treated with gelfoam soaked in phosphate buffered saline (PBS), nerve growth factor (NGF), or LIF. Neuronal nucleoli in the L5 dorsal root ganglia were counted, appropriate corrections applied, and the resultant neuronal loss expressed as a percentage of the contralateral intact side. In animals where LIF was administered neuronal loss was significantly reduced: 2 days after LIF treatment neuronal loss was 19.5% compared to 43% in PBS-treated animals; 3 days after LIF treatment neuronal loss was 20.4% compared to 40.2% in PBS-treated animals; however, 7 days after LIF treatment there was no significant reduction in the number of neurons lost. The degree of rescue of sensory neurons in vivo by LIF was found to be similar to NGF, which was not surprising as both factors supported the survival of a similar population of sensory neurons in vitro. Rescue was not observed when LIF-containing gelfoam was placed away from the axotomised nerve, suggesting that LIF's action may be associated with its retrograde transport or direct signalling at the site of nerve injury.
Cheema
S S
SS
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Richards
L
L
Murphy
M
M
Bartlett
P F
PF
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001369:Axons / Q000502:physiology*; D002466:Cell Nucleolus / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D006131:Growth Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000502:physiology / Q000648:ultrastructure
D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D009414:Nerve Growth Factors