BDNF and NT-4/5 exert neurotrophic influences on injured adult spinal motor neurons.
Adult motor neurons, like their immature antecedents, express the mRNA for the signaling receptor for brain-derived neurotrophic factor (BDNF) 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 to influence spinal motor neurons in adulthood. The present study tests if BDNF or NT-4/5 modulate the reactive responses of adult spinal motor neurons to nerve injury. We utilize sciatic nerve transection to axotomize the spinal motor neurons that form the retrodorsal lateral nucleus (RDLN) and show that, after axotomy, RDLN motor neurons lose ChAT immunoreactivity and also reexpress p75Ingfr, the low affinity receptor 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 neurons; thus, as compared to vehicle treatments, BDNF and NT-4/5 produce statistically significant increases in the optical density of ChAT immunostaining. Furthermore, BDNF and NT-4/5 also significantly increase the RDLN reexpression of p75Ingfr after sciatic nerve transection. Interestingly, essentially identical increases in RDLN ChAT and p75Ingfr immunostaining are produced by sciatic nerve crush injuries in the absence of exogenous neurotrophin treatment. These data show that treatment with exogenous BDNF and NT-4/5 changes the response of adult spinal motor neurons to sciatic nerve transection. Furthermore, these neurotrophins elicit reactive responses in axotomized motor neurons that mimic those produced by endogenous agents in regenerating crushed peripheral nerve.
Friedman
B
B
Regeneron Pharmaceuticals Inc., Tarrytown, New York 10591.
Kleinfeld
D
D
Ip
N Y
NY
Verge
V M
VM
Moulton
R
R
Boland
P
P
Zlotchenko
E
E
Lindsay
R M
RM
Liu
L
L
D000818:Animals; D001369:Axons; D019208:Brain-Derived Neurotrophic Factor; D003714:Denervation; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D009409:Nerve Crush; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology*
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C071951:neurotrophin 5; C073922:neurotrophin 4