7,8-dihydroxyflavone prevents synaptic loss and memory deficits in a mouse model of Alzheimer's disease
Bibliographic
Year of Publication:
2014
Contact PI Name:
Keqiang Ye
Primary Reference (PubMED ID):
Funding Source:
National Natural Science Foundation of China
National Institute on Aging (NIA)
Study Goal and Principal Findings:
In this study chronic oral administration of the TrkB agonist 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.
Therapeutic Agent
Therapeutic Information:
Therapeutic Notes:
Tyrosine Receptor Kinase B (TrkB) has been nominated as a potential target for AD. Nominated targets are obtained from several sources, including the National Institute on Aging's Accelerating Medicines Partnership in Alzheimer's Disease (AMP-AD) consortium. Targets have been identified using computational analyses of high-dimensional genomic, proteomic and/or metabolomic data derived from human samples. See Agora link for more information.
Animal Model
Model Information:
Experimental Design
Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest
Outcomes
Outcome Measured
Outcome Parameters
Behavioral
Morris Water Maze
Histopathology
beta Amyloid Load
Biochemical
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Immunochemistry
Synaptogenesis
Microscopy
Dendritic Spines
Electron Microscopy
Synaptic Density
Electrophysiology
Long Term Potentiation (LTP)
Cell Biology
Neuroprotection-Amyloid Neurotoxicity
Pharmacodynamics
Target Engagement (Activation Tyrosine Receptor Kinase B)