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

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

Author information

1
1] Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA [2] Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.
2
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
3
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
4
Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA.

Abstract

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.

PMID:
24022672
PMCID:
PMC3895241
DOI:
10.1038/npp.2013.243
[Indexed for MEDLINE]
Free PMC Article

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