Upregulation of GFRalpha-1 and c-ret in primary sensory neurons and spinal motoneurons of aged rats.

Aging is associated with a decline in neuromuscular and somatosensory functions. Senile muscle atrophy, considered to be of neurogenic origin, is prevalent, and sensory thresholds increase with age. However, the loss of motoneurons and primary sensory neurons is small, while sensory and motor innervation appears disturbed due to aging-related axon lesions. One mechanism which may play a role in this process is altered trophin signaling. We here report that the glial cell line-derived neurotrophic factor (GDNF) receptor GFRalpha-1 mRNA and GFRalpha-1 protein-like immunoreactivity are upregulated in spinal motoneurons, and in dorsal root ganglion neurons of 30-month-old rats. The established signaling mechanism for the GDNF/GFRalpha-1 complex is through binding to the tyrosine kinase receptor encoded by the c-ret proto-oncogene, and we also show here that c-ret mRNA is upregulated in both motoneurons and primary sensory neurons of aged rats. The findings reported here, combined with evidence presented in other studies of changes in p75(NTR) and trk receptor expressions in aging primary sensory neurons and motoneurons, point at marked alterations in trophin signaling in senescence. Copyright 1999 Wiley-Liss, Inc.