Protective effects of 7,8-dihydroxyflavone on neuropathological and neurochemical changes in a mouse model of Alzheimer's disease

Eur J Pharmacol. 2018 Jun 5;828:9-17. doi: 10.1016/j.ejphar.2018.02.045. Epub 2018 Mar 3.

Abstract

Interest in brain-derived neurotrophic factor (BDNF) was greatly enhanced when it was recognized that its expression is reduced in neurodegenerative disorders, especially in Alzheimer's disease (AD). BDNF signaling through the TrkB receptor has a central role in promoting synaptic transmission, synaptogenesis, and facilitating synaptic plasticity making the BDNF-TrkB signaling pathway an attractive candidate for targeted therapies. Here we investigated the early effect of the small molecule TrkB agonist, 7,8 dihydroxyflavone (7,8-DHF), on AD-related pathology, dendritic arborization, synaptic density, and neurochemical changes in the 5xFAD mouse model of AD. We treated 5xFAD mice with 7,8-DHF for 2 months beginning at 1 month of age. We found that, in this model of AD, 7,8-DHF treatment decreased cortical Aβ plaque deposition and protected cortical neurons against reduced dendritic arbor complexity but had no significant impact on the density of dendritic spines. In addition 7,8-DHF treatment protected against hippocampal increase in the level of choline-containing compounds and glutamate loss, but had no significant impact on hippocampal neurogenesis.

Keywords: 7,8-Dihydroxyflavone; Alzheimer's disease; Brain-derived neurotrophic factor (BDNF); Choline.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Dendritic Spines / drug effects
  • Dendritic Spines / pathology
  • Disease Models, Animal
  • Flavones / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Mice
  • Neuroprotective Agents / pharmacology*
  • Peptide Fragments / metabolism

Substances

  • 6,7-dihydroxyflavone
  • Amyloid beta-Peptides
  • Flavones
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)