Effects of brain-derived neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease.
Brain-derived neurotrophic factor (BDNF) has been shown to promote the survival of developing motor neurons in vitro and to rescue motor neurons from axotomy-induced cell death in vivo. In this study, we examined the effects of exogenous BDNF on the progression of wobbler mouse motor neuron disease (MND). After clinical diagnosis at age 3 to 4 weeks, 20 affected mice received subcutaneous injections of recombinant human BDNF (5 mg/kg, n = 10) or vehicle (n = 10), three times a week for 4 weeks. In a separate experiment done to conduct a histometric analysis of the C-5 and C-6 ventral roots and to determine the number of myelinated nerve fibers, 7 wobbler mice received identical BDNF treatment. In the 10 BDNF-treated wobbler mice, grip strength declined at a slower rate (p < 0.03) and was twice as great as that of vehicle-treated animals at the end of treatment (p < 0.01). In vivo biceps (p < 0.01) and in vitro muscle twitch tensions (p < 0.02) were also greater than those of vehicle-treated mice. The biceps muscle weight was 20% greater (p < 0.05) and the mean muscle fiber diameter was significantly larger in BDNF-treated mice (p < 0.001) because the number of small (denervated) muscle fibers was markedly reduced. The number of myelinated motor axons at the cervical ventral roots studied in the additional 7 affected mice was 25% greater with BDNF treatment (p < 0.0001). This study establishes that exogenous BDNF administration can retard motor dysfunction in a natural MND and diminish denervation muscle atrophy and motor axon loss.
Ikeda
K
K
Department of Neurology, Cleveland Clinic Foundation, OH 44195, USA.
Klinkosz
B
B
Greene
T
T
Cedarbaum
J M
JM
Wong
V
V
Lindsay
R M
RM
Mitsumoto
H
H
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D051379:Mice; D008818:Mice, Neurologic Mutants; D008854:Microscopy, Electron; D016472:Motor Neuron Disease / Q000188:drug therapy* / Q000473:pathology; D009132:Muscles / Q000473:pathology / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000627:therapeutic use*
D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins