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Improvement of spatial memory function in APPswe/PS1dE9 mice after chronic inhibition of phosphodiesterase type 4D

BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2014
Contact PI Name:
Jos Prickaerts
Contact PI Affiliation:
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, The Netherlands
Co-Authors:
A.S.R. Sierksma, D.L.A. van den Hove, F. Pfau, M. Philippens, O. Bruno, E. Fedele, R. Ricciarelli, H.W.M. Steinbusch, T. Vanmierlo
Primary Reference (PubMED ID):
24067928
Funding Source:
Internationale Stichting Alzheimer Onderzoek (ISAO)
Study Goal and Principal Findings:

In this study the authors investigated the effects of chronic GEBR-7b treatment on spatial memory function in the APPswe/PS1dE9 mouse model of AD. In particular, the authors were interested in the effects of GEBR-7b on CREB phosphorylation, BDNF signaling and postsynaptic plasticity. Additionally, the effects of GEBR-7b treatment on AD related neuropathology were assessed, including tau signaling pathways and Abeta levels. Results showed a cognition enhancing potential of GEBR-7b in APPswe/PS1dE9 mice as their spatial memory function in the object location test was improved. GEBR-7b treatment did not affect CREB phosphorylation, hippocampal brain-derived neurotrophic factor levels and synaptic densities, hippocampal GSK3b levels, tau phosphorylation or Abeta levels. In conclusion, GEBR-7b can enhance spatial memory function in the APPswe/PS1dE9 mouse model of AD. Although the underlying mechanisms of its cognition enhancing potential remain to be elucidated, PDE4D inhibition appears an interesting novel therapeutic option for cognitive deficits in AD.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
GEBR-7b
PubMed
PubChem
Patents
Therapeutic Target:
Phosphodiesterase Type 4D (PDE4D)
Open Targets
Pharos
Agora

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1
Model Name:
APPswe/PSEN1dE9 (C57BL6)
ALZFORUM
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
Elevated Zero Maze
Open Field Test
Y Maze
Nesting Behavior
Forced Swim Test
Biochemical
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
CREB/phospho-CREB
Synaptophysin
Postsynaptic Density Protein 95 (PSD95)
phospho-Tau
GSK3 beta/phospho-GSK3 beta
Brain-Derived Neurotrophic Factor (BDNF)
Toxicology
Body Weight
Food Intake
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