7,8-Dihydroxyflavone improves motor performance and enhances lower motor neuronal survival in a mouse model of amyotrophic lateral sclerosis

Neurosci Lett. 2014 Apr 30:566:286-91. doi: 10.1016/j.neulet.2014.02.058. Epub 2014 Mar 15.

Abstract

Amyotrophic lateral sclerosis (ALS) is an enigmatic neurodegenerative disorder without any effective treatment characterized by loss of motor neurons (MNs) that results in rapidly progressive motor weakness and early death due to respiratory failure. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family known to play a prominent role in the differentiation and survival of MNs. The flavonoid 7,8-dihydroxyflavone (7,8-DHF) is a potent and selective small molecule tyrosine kinase receptor B (TrkB) agonist that mimics the effects of BDNF. In the present study, we evaluated the neuroprotective effects of 7,8-DHF in a transgenic ALS mouse model (SOD1(G93A)). We found that chronic administration of 7,8-DHF significantly improved motor deficits, and preserved spinal MNs count and dendritic spines in SOD1(G93A) mice. These data suggest that 7,8-DHF should be considered as a potential therapy for ALS and the other motor neuron diseases.

Keywords: 7,8-Dihydroxyflavone; Amyotrophic lateral sclerosis; BDNF; Motor neurons; TrkB.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / pathology
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Cell Count
  • Cell Survival / drug effects
  • Dendritic Cells / drug effects
  • Dendritic Cells / pathology
  • Flavanones / pharmacology*
  • Flavanones / therapeutic use
  • Humans
  • Mice, Transgenic
  • Motor Neurons / drug effects*
  • Motor Neurons / pathology
  • Motor Skills / drug effects
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Receptor, trkB / agonists*
  • Spinal Cord / drug effects
  • Spinal Cord / pathology
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase-1

Substances

  • 7,8-dihydroxyflavanone
  • Flavanones
  • Neuroprotective Agents
  • SOD1 protein, human
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Receptor, trkB