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Inhibition of PKA attenuates memory deficits induced by β-amyloid (1-42), and decreases oxidative stress and NF-κB transcription factors


Year of Publication:
Contact PI Name:
Mohammad Sharifzadeh
Contact PI Affiliation:
Department of Pharmacology and Toxicology, Pharmaceutical Sciences research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Bahareh Eftekharzadeh, Mahmoudreza Ramin, Fariba Khodagholi, Shahla Moradi, Kaveh Tabrizian, Rojin Sharif, Kian Azami, Cordian Beyer
Primary Reference (PubMED ID):
Funding Source:
Shahid Beheshti University of Medical Sciences, Tehran, Iran
Tehran University of Medical Science, Iran
Study Goal and Principal Findings:

Alzheimer’s disease (AD), the most relevant cause of dementia in elderly, is characterized by amyloidβ (Aβ) containing plaques and neurofibrillatory tangles, synaptic and neurona  loss, along with progressive cognitive impairment in short-term memory. However, mechanistic links between protein kinase A (PKA), oxidative stress and memory loss in response to Aβ remain elusive. In the present study, is examined the effects of post-training bilateral intra-hippocampal infusions of the specific protein kinase AII inhibitor, H-89, on memory deficits induced by Aβ (1–42) in Aβ-pretreated rats. H-89 and Aβ were administered immediately after completion of training. All animals were trained for 4 consecutive days and tested 9 and 19 days after the infusions. Significant differences were observed in the time and distance of finding the hidden platform in Aβ treated animals after 19 days. Interestingly, intra-hippocampal infusion of H-89 (5 M/side) significantly prevented the Aβ-induced memory impairment. Furthermore, evaluation of NFB (nuclear factor-B), and antioxidant enzymes, such as γ-GCS (glutamylcysteine synthetase), HO-1 (hemeoxygenase-1), GSH (glutathione), and SOD (superoxide dismutase) confirmed the protective effect of H-89. Given the possible neuroprotective effects of H-89 on A-induced memory impairment, our results may open a new avenue for the prevention of AD by PKAII signaling pathway inhibitor.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
H-89 Dihydrochloride
Therapeutic Target:
Protein Kinase A (PKA)

Animal Model

Model Information:
Model Type:
beta Amyloid Peptide Injection
Strain/Genetic Background:
Not Applicable

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
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


Outcome Measured
Outcome Parameters
Morris Water Maze
Glutathione (GSH)
Superoxide Dismutase (SOD)
Nuclear Factor kappa B (NFkB)
Heme Oxygenase 1 (HO1)
gamma Glutamylcysteine Synthetase (GCS)
Caspase 3