BDNF AND NT-4 5 EXERT NEUROTROPHIC INFLUENCES ON INJURED ADULT SPINALMOTOR-NEURONS/

Adult motor neurons, like their immature antecedents, express the mRNA for the signaling receptor for brain-derived neurotrophic factor (BDN F) and for neurotrophin-4/5 (NT-4/5). However, while both BDNF and NT- 4/5 support the survival of axotomized developing spinal motor neurons in vitro or in vivo, it is not known whether these factors continue t o influence spinal motor neurons in adulthood. The present study tests if BDNF or NT-4/5 modulate the reactive responses of adult spinal mot or neurons to nerve injury. We utilize sciatic nerve transection to ax otomize the spinal motor neurons that form the retrodorsal lateral neu rons (RDLN) and show that, after axotomy, RDLN motor neurons lose ChAT immunoreactivity and also, reexpress p75(lngfr) the low affinity rece ptor for all neurotrophin family members. Treatment with BDNF or NT-4/ 5 alters these effects of sciatic nerve transection. Both BDNF and NT- 4/5 attenuate the loss of ChAT expression in axotomized RDLN motor neu rons; thus, as compared to vehicle treatments, BDNF and NT-4/5 produce statistically significant increases in the optical density of ChAT im munostaining. Furthermore, BDNF and NT-4/5 also significantly increase the RDLN reexpression of p75(lngfr) after sciatic nerve transection. Interestingly, essentially identical increases in RDLN ChAT and p75(ln gfr) immunostaining are produced by sciatic nerve crush injuries in th e absence of exogenous neurotrophin treatment. These data show that tr eatment with exogenous BDNF and NT-4/5 changes the response of adult s pinal motor neurons to sciatic nerve transection. Furthermore, these n eurotrophins elicit reactive responses in axotomized motor neurons tha t mimic those produced by endogenous agents in regenerating crushed pe ripheral nerve.