Effect of Ouabain on Glutamate Transport in the Hippocampus of Rats with LPS-Induced Neuroinflammation

Author(s)

Garcia, Israel Jose Pereira ; Kinoshita, Paula Fernanda ; Valadares, Jessica Martins de Moura ; de Carvalho, Luciana Estefani Drumond ; Cortes, Vanessa Faria ; Barbosa, Leandro Augusto ; Scavone, Cristoforo ; Santos, Herica de Lima

• Document type: Journal article
• Source: BIOMEDICINES; v. 11, n. 3, p. 15-pg., 2023-03-01.

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 mu g/kg), saline (CTR), LPS (200 mu g/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 alpha 1, alpha 2, and alpha 3 isoforms of Na,K-ATPase and the glutamate transporters, EAAT1 and EAAT2, were also analysed. Treatment with OUA caused a specific increase in the alpha 2 isoform expression (similar to 20%), whereas LPS decreased its expression (similar to 22%), and treatment with OUA before LPS prevented the effects of LPS. Moreover, LPS caused a decrease of approximately 50% in GS activity compared with that in the CTR group; however, OUA pre-treatment attenuated this effect of LPS. Notably, it was found that treatment with OUA caused an increase in the expression of EAAT1 (similar to 30%) and EAAT2 (similar to 25%), whereas LPS caused a decrease in the expression of EAAT1 (similar to 23%) and EAAT2 (similar to 25%) compared with that in the CTR group. When treated with OUA, the effects of LPS were abrogated. In conclusion, the OUA pre-treatment abolished the effect caused by LPS, suggesting that this finding may be related to the restoration of the interaction between FXYD2 and the studied membrane proteins. (AU)

• FAPESP's process: 16/07427-8 - Aging and neuroprotection: effects of Klotho protein in energetic metabolism, Na,K-ATPase signaling and adaptative response in central nervous system
• Grantee: Cristoforo Scavone
• Support Opportunities: Research Projects - Thematic Grants