Effect of ouabain on glutamate transport in the hippocampus of rats with LPS-induced neuroinflammation

Abstract

Abstract A lipopolysaccharide (LPS)-induced neuroinflammation rat model was used to study the effects of ouabain (OUA) at low concentrations, which can interact with the Na, K-ATPase, causing the modulation of intracellular signalling pathways in the central nervous system. Our study aimed to analyse the effects of OUA on glutamate transport in the hippocampus of rats with LPS-induced neuroinflammation. Adult male Wistar rats were divided into four groups: OUA (1.8 µg/kg), saline (CTR), LPS (200 µg/kg), and OUA + LPS (OUA 20 min before LPS). The animals were sacrificed after 2 h, and the hippocampus was collected for analysis. After treatment, we determined the activities of Na, K-ATPase and glutamine synthetase (GS). In addition, expression of the α1, α2, and α3 isoforms of Na, K-ATPase and the glutamate transporters, EAAT1 and EAAT2, were also analysed. Analysis of the expression of the α-isoform of the Na, K-ATPase revealed that treatment with OUA caused an increase in α2 isoform expression (~ 20%), whereas LPS decreased its expression (~ 22%), and the OUA pre-treatment prevented the deleterious effect of LPS. Moreover, LPS caused a decrease of approximately 50% in GS activity compared to that in the CTR group; however, OUA pre-treatment attenuated the LPS effect. Notably, it was found that treatment with OUA caused an increase in the expression of EAAT1 (~ 30%) and EAAT2 (~ 25%), whereas LPS caused a decrease in the expression of EAAT1 (~ 23%) and EAAT2 (~ 25%) compared to that in the CTR group. However, OUA pre-treatment abrogated the effect of LPS. OUA also interacts with FXYD2 and glutamate transporters. Our data suggest a neuroprotective effect of OUA against LPS-induced injury in the rat hippocampus.