PMID- 11268018
OWN - NLM
STAT- MEDLINE
DCOM- 20010419
LR  - 20190915
IS  - 0148-639X (Print)
IS  - 0148-639X (Linking)
VI  - 24
IP  - 4
DP  - 2001 Apr
TI  - Role of brain-derived neurotrophic factor in wobbler mouse motor neuron disease.
PG  - 474-80
AB  - Brain-derived neurotrophic factor (BDNF) is neuroprotective for motoneurons 
      undergoing degeneration, including those in natural motor neuron disease (MND) in 
      wobbler mice. To assess the role of BDNF in this model of MND, endogenous BDNF 
      immunoreactivity was analyzed by semiquantitative video-image analysis. Affected 
      cervical spinal cord motoneurons had significantly greater BDNF immunoreactivity 
      compared to motoneurons of healthy littermates (P = 0.01) and affected lumbar 
      spinal cord motoneurons (P = 0.008 at age 4 weeks; P = 0.005 at age 8 weeks). 
      Neuronal nitric oxide synthase (n-NOS) immunocytochemistry revealed increased 
      immunoreactivity in the affected cervical spinal cord motoneurons. Exogenous BDNF 
      treatment partially inhibited the increased NOS activity, as quantitatively 
      measured by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) 
      histochemistry. The mean number of NADPH-d(+) motoneurons in the cervical 
      anterior horn decreased from 3.5 +/- 1.2 to 1.5 +/- 1.2 (P = 0.002). The increase 
      in endogenous BDNF immunoreactivity in the affected spinal cord may be 
      compensatory in diseased motoneurons, yet it appears to still be inadequate 
      because exogenous BDNF treatment is required to suppress increased NOS activity 
      in degenerating motoneurons. Our study indicates that BDNF is important in 
      halting nitric oxide (NO)-mediated motor neuron degeneration, which has potential 
      implications for the treatment of neurodegenerative disorders.
CI  - Copyright 2001 John Wiley & Sons, Inc.
FAU - Tsuzaka, K
AU  - Tsuzaka K
AD  - Department of Neurology and Neurosciences, Cleveland Clinic Foundation, 
      Cleveland, Ohio, USA.
FAU - Ishiyama, T
AU  - Ishiyama T
FAU - Pioro, E P
AU  - Pioro EP
FAU - Mitsumoto, H
AU  - Mitsumoto H
LA  - eng
GR  - K08-NS01846-03/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Muscle Nerve
JT  - Muscle & nerve
JID - 7803146
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.14.13.39 (Nos1 protein, mouse)
RN  - EC 1.6.99.1 (NADPH Dehydrogenase)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/*metabolism
MH  - Cell Count
MH  - Disease Models, Animal
MH  - Immunohistochemistry
MH  - Injections, Intramuscular
MH  - Mice
MH  - Mice, Neurologic Mutants
MH  - Motor Neuron Disease/genetics/*metabolism/pathology
MH  - Motor Neurons/metabolism/pathology
MH  - NADPH Dehydrogenase/metabolism
MH  - Nitric Oxide Synthase/metabolism
MH  - Nitric Oxide Synthase Type I
MH  - Spinal Cord/enzymology/pathology
EDAT- 2001/03/27 10:00
MHDA- 2001/04/21 10:01
CRDT- 2001/03/27 10:00
PHST- 2001/03/27 10:00 [pubmed]
PHST- 2001/04/21 10:01 [medline]
PHST- 2001/03/27 10:00 [entrez]
AID - 10.1002/mus.1029 [pii]
AID - 10.1002/mus.1029 [doi]
PST - ppublish
SO  - Muscle Nerve. 2001 Apr;24(4):474-80. doi: 10.1002/mus.1029.