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Erythropoietin improves synaptic plasticity and memory deficits by decrease of the neurotransmitter release probability in the rat model of Alzheimer's disease

Bibliographic

Year of Publication:
2015
Contact PI Name:
Masoud Haghani
Contact PI Affiliation:
Department of physiology, Shiraz University of Medical Sciences, Shiraz, Iran
Co-Authors:
Parisa Esmaeili Tazangi, Seyed Mostafa Shid Moosavi, Mohamad Shabani
Primary Reference (PubMED ID):
Funding Source:
Research Council of Shiraz University of Medical Sciences, Iran
Study Goal and Principal Findings:

Introduction: Several studies indicate erythropoietin (Epo) to have remarkable neuroprotection in various central nervous system disorders, including Alzheimer's disease (AD). Amyloid beta (Aβ) is believed to be responsible for the synaptic dysfunction that occurs in AD. Therefore, the present study is aimed to investigate the effects of Epo on the Aβ-induced impairments in learning-memory and hippocampal synaptic plasticity.

Materials and methods: Male Sprague-Dawley rats (200-250 g) were used in this study. After the injection of Aβ, they were injected intra-peritoneal with Epo in the Aβ+Epo group or its vehicle in the Aβ+V group every other day for 12 days. A shuttle box apparatus was used for the passive avoidance learning and memory study. Moreover, paired-pulse ratio (PPR) was monitored before and after tetanic stimulation.

Results: Bilateral injection of Aβ decreased step-through latency (STL), whereas the 12 day administration of Epo significantly improved memory performance in Aβ+Epo group. The field potential recording demonstrated that the in vivo administration of Aβ25-35 led to extreme inhibition in long-term potentiation, this inhibition was accompanied by a significant increase of the normalized PPR (PPR after HFS/PPR before HFS) as an index for release probability. However, administration of Epo recovers the magnitude of the LTP and the extent of normalized PPR.

Conclusion: The results of this study demonstrated that the injection of Aβ25-35 resulted in impaired LTP and the memory process, which is likely mediated through increasing the release probability of neurotransmitter vesicles. In addition, treatment with Epo improved the Aβ-induced deficits in memory and LTP induction, probably via recovering the release probability.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Peptide
Therapeutic Agent:
Erythropoietin
Therapeutic Target:
Erythropoietin Receptor

Animal Model

Model Information:
Species:
Rat
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
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
Passive Avoidance Test
Electrophysiology
Long Term Potentiation (LTP)
Paired-Pulse Ratio (PPR)
field Excitatory Postsynaptic Potential (fEPSP)
Physiology
Hematocrit