Effects of brain-derived neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease.

Abstract

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.

• Authors: K Ikeda, B Klinkosz, T Greene, J M Cedarbaum, V Wong, R M Lindsay, H Mitsumoto
• Journal: Annals of neurology (Ann Neurol) Vol. 37 Issue 4 Pg. 505-11 (Apr 1995) ISSN: 0364-5134 [Print] United States
• PMID: 7717687 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Brain-Derived Neurotrophic Factor
• Nerve Tissue Proteins

Topics

• Animals
• Brain-Derived Neurotrophic Factor
• Mice
• Mice, Neurologic Mutants
• Microscopy, Electron
• Motor Neuron Disease (drug therapy, pathology)
• Muscles (pathology, ultrastructure)
• Nerve Tissue Proteins (therapeutic use)