Methionine-free brain-derived neurotrophic factor in wobbler mouse motor neuron disease: dose-related effects and comparison with the methionyl form.
We compared the clinical and pharmacodynamic effects of N-terminal methionine brain-derived neurotrophic factor (met-BDNF) and endogenous met-free BDNF in wobbler mouse motor neuron disease (MND). Met- or met-free BDNF at 5 or 20 mg/kg was subcutaneously injected daily, six times/week for 4 weeks. At 20 mg/kg, grip strength (P<0.05, met-free BDNF; P<0.01, met-BDNF) and running speed (P<0.01 for both groups) improved compared to vehicle. At 5 mg/kg, the beneficial effect was more modest. Plasma BDNF levels after the final injection were dose-dependent and did not differ between BDNF groups. Endogenous met-free BDNF exerts effects similar to met-BDNF in wobbler MND.
Ishiyama
Takeo
T
Department of Neurology and Neuroscience, The Cleveland Clinic Foundation, Cleveland, OH, USA.
Ogo
Hiroki
H
Wong
Vivian
V
Klinkosz
Bogdan
B
Noguchi
Hiroshi
H
Nakayama
Chikao
C
Mitsumoto
Hiroshi
H
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008715:Methionine / Q000172:deficiency*; D051379:Mice; D008818:Mice, Neurologic Mutants; D016472:Motor Neuron Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018908:Muscle Weakness / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine