7,8-dihydroxyflavone prevents synaptic loss and memory deficits in a mouse model of Alzheimer's disease

Neuropsychopharmacology. 2014 Feb;39(3):638-50. doi: 10.1038/npp.2013.243. Epub 2013 Sep 11.


Synaptic loss in the brain correlates well with disease severity in Alzheimer disease (AD). Deficits in brain-derived neurotrophic factor/tropomyosin-receptor-kinase B (TrkB) signaling contribute to the synaptic dysfunction of AD. We have recently identified 7,8-dihydroxyflavone (7,8-DHF) as a potent TrkB agonist that displays therapeutic efficacy toward various neurological diseases. Here we tested the effect of 7,8-DHF on synaptic function in an AD model both in vitro and in vivo. 7,8-DHF protected primary neurons from Aβ-induced toxicity and promoted dendrite branching and synaptogenesis. Chronic oral administration of 7,8-DHF activated TrkB signaling and prevented Aβ deposition in transgenic mice that coexpress five familial Alzheimer's disease mutations (5XFAD mice). Moreover, 7,8-DHF inhibited the loss of hippocampal synapses, restored synapse number and synaptic plasticity, and prevented memory deficits. These results suggest that 7,8-DHF represents a novel oral bioactive therapeutic agent for treating AD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease* / complications
  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / pathology
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Antipsychotic Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Disease Models, Animal
  • Female
  • Flavones / therapeutic use*
  • Hippocampus / pathology
  • Humans
  • In Vitro Techniques
  • Maze Learning / drug effects
  • Memory Disorders / etiology*
  • Memory Disorders / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics
  • Neurons / drug effects
  • Neurons / pathology
  • Neurons / ultrastructure
  • Plaque, Amyloid / pathology
  • Synapses / drug effects
  • Synapses / pathology*


  • 6,7-dihydroxyflavone
  • Amyloid beta-Protein Precursor
  • Antipsychotic Agents
  • Flavones