Up-regulation of GDNFR-alpha and c-ret mRNA in facial motor neurons following facial nerve injury in the rat.
Glial cell line-derived neurotrophic factor (GDNF), a powerful trophic factor for developing, and injured adult motor neurons, has recently been shown to mediate its physiological effects via a multi-component receptor system comprising the GDNFR-alpha binding protein and the c-ret receptor tyrosine kinase. Using in situ hybridization histochemistry this study investigated whether adult motor neurons express mRNAs encoding GDNFR-alpha and c-ret, and explored possible time-dependent changes in these mRNA species following facial nerve resection and crush injury. Levels of mRNA for the signaling component of the GDNF receptor, c-ret, were increased approximately 1.4-fold in the ipsilateral facial nucleus, 1 and 3 days after unilateral facial nerve crush and resection, but returned to contralateral levels by 7-21 days. GDNFR-alpha mRNA was increased from 2 to 3-fold in the facial nucleus at 1 and 3 days after facial nerve crush and to similar, but more sustained (up to 21 days), levels after resection. In contrast, GDNF mRNA was not detectable in normal or injured facial motor neurons. The gradual return of c-ret and GDNFR-alpha mRNAs to control levels 21 days after facial nerve crush, parallels the axonal regeneration process, while nerve damage by resection has more severe consequences compared to nerve crush, reflected by the prolonged time course of increased GDNFR-alpha mRNA, similar to markers such as the NGF-receptor, galanin and GAP-43. These findings confirm the importance of GDNF trophic/signaling systems after nerve injury and suggest the potential for broad biological and therapeutic actions of GDNF or related factors in the CNS, particularly on damaged motor neurons.