7,8-Dihydroxyflavone improves memory consolidation processes in rats and mice

Behav Brain Res. 2013 Nov 15;257:8-12. doi: 10.1016/j.bbr.2013.09.029. Epub 2013 Sep 23.


Brain-derived neurotrophic factor (BDNF) is a crucial regulator of neuronal survival and neuroplasticity in the central nervous system (CNS). As a result, there has been a growing interest in the role of BDNF in neuropsychiatric disorders associated with neurodegeneration, including depression and dementia. However, until now, BDNF-targeting therapies have yielded disappointing results. BDNF is thought to exert its beneficial effects on synaptic and neuronal plasticity mainly through binding to the tyrosine kinase B (TrkB) receptor. Recently, 7,8-dihydroxyflavone (7,8-DHF) was identified as the first selective TrkB agonist. In the present study the effect of 7,8-DHF on memory consolidation processes was evaluated. In healthy rats, 7,8-DHF improved object memory formation in the object recognition task when administered both immediately and 3h after learning. In a transgenic mouse model of Alzheimer's disease, i.e. APPswe/PS1dE9 mice, spatial memory as measured in the object location task was improved after administration of 7,8-DHF. A similar memory improvement was found when their wild-type littermates were treated with 7,8-DHF. The acute beneficial effects in healthy mice suggest that effects might be symptomatic rather than curing. Nevertheless, this study suggests that 7,8-DHF might be a promising therapeutic target for dementia.

Keywords: 7,8-DHF; 7,8-Dihydroxyflavone; 7,8-dihydroxyflavone; AD; Alzheimer's disease; Aβ; BDNF; Brain-derived neurotrophic factor; CNS; CREB; Ca(2+)/calmodulin-dependent protein kinase II; CaMKII; Cognition enhancers; LTP; Memory consolidation; N-methyl-d-aspartic acid; NMDA; OLT; ORT; PTSD; T1; T2; TrkB; TrkB receptor; WT; amyloid beta; brain-derived neurotrophic factor; cAMP-responsive element binding; central nervous system; first trial; i.p.; intraperitoneal; long-term potentiation; mBDNF; mature BDNF; object location task; object recognition task; p.o.; per os; post-traumatic stress disorder; precursor of BDNF; proBDNF; second trial; tyrosine kinase B; wild-type.

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Flavanones / therapeutic use*
  • Humans
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics
  • Presenilin-1 / genetics
  • Rats
  • Rats, Wistar
  • Receptor, trkB / agonists*
  • Recognition, Psychology / drug effects


  • 7,8-dihydroxyflavanone
  • Amyloid beta-Protein Precursor
  • Flavanones
  • PSEN1 protein, human
  • Presenilin-1
  • Receptor, trkB