Differential regulation of trophic factor receptor mRNAs in spinal motoneurons after sciatic nerve transection and ventral root avulsion in the rat

After sciatic nerve lesion in the adult rat, motoneurons survive and regene rate, whereas the same lesion in the neonatal animal or an avulsion of vent ral roots from the spinal cord in adults induces extensive cell death among lesioned motoneurons with limited or no axon regeneration. A number of sub stances with neurotrophic effects have been shown to increase survival of m otoneurons in vivo and in vitro. Here we have used semiquantitative in situ hybridization histochemistry to detect the regulation in motoneurons of mR NAs for receptors to ciliary neurotrophic factor (CNTF), leukemia inhibitor y factor (LIF), glial cell line-derived neurotrophic factor (GDNF), brain-d erived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) 1-42 days afte r the described three types of axon injury. After all types of injury, the mRNAs for GDNF receptors (GFR alpha-1 and c-RET) and the LIF receptor LIFR were distinctly (up to 300%) up-regulated in motoneurons. The CNTF receptor CNTFR alpha mRNA displayed only small changes, whereas the mRNA for membra ne glycoprotein 130 (gp130), which is a critical receptor component for LIF and CNTF transduction, was profoundly down-regulated in motoneurons after ventral root avulsion. The BDNF full-length receptor trkB mRNA was up-regul ated acutely after adult sciatic nerve lesion, whereas after ventral root a vulsion trkB was down-regulated. The NT-3 receptor trkC mRNA was strongly d own-regulated after ventral root avulsion. The results demonstrate that rem oval of peripheral nerve tissue from proximally lesioned motor axons induce s profound down-regulations of mRNAs for critical components of receptors f or CNTF, LIF, and NT-3 in affected motoneurons, but GDNF receptor mRNAs are up-regulated in the same situation. These results should be considered in relation to the extensive cell death among motoneurons after ventral root a vulsion and should also be important for the design of therapeutical approa ches in cases of motoneuron death. J. Comp. Neurol. 426:587-601, 2000. (C) 2000 Wiley-Liss, Inc.