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


BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2014
Contact PI Name:
Keqiang Ye
Contact PI Affiliation:
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
Co-Authors:
Zhentao Zhang, Xia Liu, Jason P Schroeder, Chi-Bun Chan, Mingke Song, Shan Ping Yu, David Weinshenker
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:
Therapy Type:
Small Molecule
Therapeutic Agent:
7,8-dihydroxyflavone (7,8-DHF)
Therapeutic Target:
Tyrosine Receptor Kinase B (TrkB)

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1
Strain/Genetic Background:
C57BL/6

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)

Source URL: http://alzped.nia.nih.gov/78-dihydroxyflavone-prevents-0