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7,8-dihydroxyflavone prevents synaptic loss and memory deficits in a mouse model of Alzheimer's disease.
- Source :
-
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2014 Feb; Vol. 39 (3), pp. 638-50. Date of Electronic Publication: 2013 Sep 11. - Publication Year :
- 2014
-
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.
- Subjects :
- Amyloid beta-Protein Precursor genetics
Animals
Cells, Cultured
Cerebral Cortex cytology
Disease Models, Animal
Female
Hippocampus pathology
Humans
In Vitro Techniques
Maze Learning drug effects
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutation genetics
Neurons drug effects
Neurons pathology
Neurons ultrastructure
Plaque, Amyloid pathology
Synapses drug effects
Alzheimer Disease complications
Alzheimer Disease drug therapy
Alzheimer Disease pathology
Antipsychotic Agents therapeutic use
Apoptosis drug effects
Flavones therapeutic use
Memory Disorders etiology
Memory Disorders prevention & control
Synapses pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1740-634X
- Volume :
- 39
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 24022672
- Full Text :
- https://doi.org/10.1038/npp.2013.243