Expression of erythropoietin receptor protein in the mouse hippocampus in response to normobaric hypoxia

Background: Over the past decades, accumulating research on erythropoietin (EPO) and its receptor (EPOR) has revealed various neuroprotective actions and upregulation in hypoxic conditions. To our knowledge, EPOR protein levels in the hippocampus and isocortex have never been measured. Therefore, the aim of this study was to measure EPOR protein in the hippocampus (HPC) and prefrontal cortex (PFC). Further objectives were to examine the effects of exposure to normobaric hypoxia of various degrees and durations on EPOR protein and to explore how longlasting these effects were. Method: Adult C57BL/6 mice were randomized into a control group (N = 12) or various hypoxia groups (N = 5-11). Mice were exposed to three different O2 concentrations (10 %, 12 %, or 18 %) for 8 h a day for 5 days and sacrificed immediately after the last exposure. The effect of exposure to 12 % O2 for 1 day and 4 weeks (8 h per day) at this survival time was also examined. Additionally, groups of mice were exposed to 12 % O2 for 1 or 5 days (8 h per day) and euthanized at various times (up to 3 weeks) thereafter to examine the duration of EPOR protein regulation in the HPC and the PFC. EPOR protein was detected with a sandwich-ELISA method. Results: EPOR protein was present in the HPC and PFC, at 206.64 +/- 43.98 pg/mg and 184.25 +/- 48.21 pg/mg, respectively. The highest increase in EPOR protein was observed in the HPC after 5 days of 8 h exposure to 12 % O2 and was most pronounced 24 h after last exposure. The effect of hypoxia normalized within one week after the last exposure. Conclusion: This study successfully measured hippocampal EPOR protein and showed a significant association between normobaric hypoxia and acute EPOR elevation. It is our hope that this study can provide guidance to future research on the neuroprotective effects of EPO.