Effect of transforming growth factor beta 1 on spinal motor neurons after axotomy

Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor beta (TGF-beta) family, has potent effects on developing motor neurons. TGF are pluripotent cytokines that exert biological effects on a variety of neurons. TGF beta 1, on the other hand, promotes motor neuron survival in vitro and saves motor neurons from naturally occurring cell death. Here we investigate the neurotrophic effects of TGF beta 1 for axotomized motor neuron death. The sciatic nerve was cut in newborn rats and TGF beta 1 was injected, either by intraperitoneally or by lesion site, for 14 days after transection. Two or six weeks postlesion, the number and the diameter of motor neurons was assessed. TGF beta 1 significantly attenuated axotomy induced motor neuron death by intraperitoneal administration or by lesion site administration at 2 weeks after neonatal axotomy in a similar way. However, no effect was observed at 6 weeks after nerve lesion, despite continuous application of TGF beta 1 daily for 14 days. These results indicate that TGF beta 1 can prevent the death of motor neurons in vivo, but it cannot permanently rescue lesioned motor neurons.