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

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.