Several lines of evidence indicate that adult neurons remain dependent on neurotrophins and that changes in tissue expression of neurotrophins and/or their receptors may play a role in senile neurodegeneration. We have studied the expression of p75NTR, trkB and trkC, respectively, in lumbar motoneurons of young adult (2-3 months) and aged (30 months) rats subjected to sciatic transection using in situ hybridization and immunohistochemistry. Nonmanipulated age-matched animals were processed in parallel. In nonmanipulated aged rats, high levels of p75NTR could be seen in a number of motoneurons (10-15%), while in young adult animals no p75NTR could be detected. Seven days following sciatic axotomy, a conspicuous ipsilateral upregulation p75NTR was observed in young adult rats. Also in aged rats there was a marked ipsilateral increase in number of p75NTR expressing neurons ( approximately 100%). In comparison to young adult rats, aged rats showed a decreased expression of both trkB (5/6 animals) and trkC (6/6 animals). Furthermore, in response to sciatic transection, 3 out of 5 aged rats did not show an increased expression of trkB. In aged rats, axotomy did not induce any significant change in trkC expression. In the young adult rats, we recorded a side-to-side effect with lower values ipsilaterally, however, it cannot be excluded that this difference was caused by an upregulation in the contralateral motoneurons. Oligonucleotide probes against BDNF and NT3 mRNA showed only very few faintly positive neurons in both age groups. Our results indicate that the pattern of regulatory changes of NT receptors in response to axotomy is different in aged and young adult rats. The lack of covariation between p75NTR and trkB and trkC regulation in aged rats indicates a changed role for p75NTR in senescent motoneurons.
Copyright 1999 Elsevier Science B.V.