Abstract 014: Impact of Placental Ischemia on Hippocampal Asic2a and Glutamate Receptor Protein Expression in Mice

Abstract

Preeclampsia (PE) is a pregnancy condition occurring in the 3 rd trimester with phenotypes such as hypertension, proteinuria, and seizures (in eclampsia). Our lab previously showed that placental ischemia, used to mimic PE, induces increased sensitivity to drug-induced seizures in rats; however, the underlying mechanisms are unknown. Acid sensing ion channels (ASICs), proton-gated ion channels, have been shown to reduce the prolonged effects of seizures and respond to pH changes within tissues. It is possible that reduced hippocampal ASIC, specifically ASIC2a, may contribute to increased seizure severity following placental ischemia. In this study, we investigated whether placental ischemia reduces ASIC2a, NMDAR1, and NMDAR2 protein expression in mouse hippocampal tissues. C57BL/6 female mice, aged 8-12wks, were randomly assigned to Sham (n=6) or reduced uterine perfusion pressure (RUPP, n=5) groups. At day 14 of pregnancy, mice underwent Sham or RUPP surgery (total ligation of uterine artery between ovary and first pup) or no ligation (Sham). Protein expression levels in placenta (ASIC2a) and hippocampus (ASIC2a, NMDAR1, and NMDAR2B) were assessed using Western blot and Image Lab software. Differences in expression were analyzed using unpaired t-tests. Placental ischemia led to reduced live pups (8±1 vs 5±1; p=0.0499) and increased hematocrit in surviving pups (30.3±1.5 vs 34.6±1.6%; p=0.0295). There was no difference in body weight (39.2±2.4 vs. 37.8±1.4g; p=0.52) or placental weight (0.09±0.01 vs. 0.10±0.004g; p=0.63) between groups. Placental ischemic mice had reduced ASIC2a levels in hippocampus (1.0±0.2 vs. 0.5±0.1; p=0.02) but not placenta (1.0±0.2 vs. 0.7±0.1; p=0.07) compared to Shams. There was no difference in expression of hippocampal NMDAR1 (1.0±0.3 vs. 1.1±0.1; p=0.84) or NMDAR2B (1.0±0.2 vs. 1.1±0.1 p=0.68) between groups. Our findings support the hypothesis that RUPP-induced increases in seizure susceptibility occurs through reduced hippocampal ASIC2a expression. Whether other ASIC subunits are decreased in the hippocampus following placental ischemia is not known. Additionally, studies assessing whether reduced ASIC2a contributes to increased seizure susceptibility are ongoing.