Signaling function of Na,K-ATPase induced by ouabain against LPS as an inflammation model in hippocampus

• Published in: Journal of neuroinflammation 2014-12, Vol.11 (1), p.218-218, Article 218
• Main Authors: Kinoshita, Paula Fernanda, Yshii, Lidia Mitiko, Vasconcelos, Andrea Rodrigues, Orellana, Ana Maria Marques, Lima, Larissa de Sá, Davel, Ana Paula Couto, Rossoni, Luciana Venturini, Kawamoto, Elisa Mitiko, Scavone, Cristoforo
• Format: Article
• Language: English
• Subjects: Adenosine; Alzheimer's disease; Analysis; Animals; Ataxia; Brain research; Brain-derived neurotrophic factor; Colleges & universities; Data analysis; Disease Models, Animal; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacology; Enzymes; Epidermal growth factor; Hearing loss; Hippocampus - drug effects; Hippocampus - immunology; Inflammation - chemically induced; Inflammation - drug therapy; Lipopolysaccharides - immunology; Male; Mitogens; Nervous system; Ouabain - administration & dosage; Ouabain - pharmacology; Physiological aspects; Potassium; Proteins; Rats; Rats, Wistar; Rodents; Signal Transduction - drug effects; Signal Transduction - immunology; Sodium-Potassium-Exchanging ATPase - drug effects; Sodium-Potassium-Exchanging ATPase - immunology; Transcription factors; Variance analysis
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-014-0218-z

Ouabain (OUA) is a newly recognized hormone that is synthesized in the adrenal cortex and hypothalamus. Low doses of OUA can activate a signaling pathway by interaction with Na,K-ATPase, which is protective against a number of insults. OUA has central and peripheral anti-inflammatory effects. Lipopolysaccharide (LPS), via toll-like receptor 4 activation, is a widely used model to induce systemic inflammation. This study used a low OUA dose to evaluate its effects on inflammation induced by LPS injection in rats. Adult male Wistar rats received acute intraperitoneal (ip) OUA (1.8 μg/kg) or saline 20 minutes before LPS (200 μg/kg, ip) or saline injection. Some of the animals had their femoral artery catheterized in order to assess arterial blood pressure values before and after OUA administration. Na,K-ATPase activity, cytokine mRNA levels, apoptosis-related proteins, NF-κB activation brain-derived neurotrophic factor BDNF, corticosterone and TNF-α levels were measured. OUA pretreatment decreased mRNA levels of the pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS) and IL-1β, which are activated by LPS in the hippocampus, but with no effect on serum measures of these factors. None of these OUA effects were linked to Na,K-ATPase activity. The involvement of the inflammatory transcription factor NF-κB in the OUA effect was indicated by its prevention of LPS-induced nuclear translocation of the NF-κB subunit, RELA (p65), as well as the decreased cytosol levels of the NF-κB inhibitor, IKB, in the hippocampus. OUA pretreatment reversed the LPS-induced glial fibrillary acidic protein (GFAP) activation and associated inflammation in the dentate gyrus. OUA also prevented LPS-induced increases in the hippocampal Bax/Bcl2 ratio suggesting an anti-apoptotic action in the brain. Our results suggest that a low dose of OUA has an important anti-inflammatory effect in the rat hippocampus. This effect was associated with decreased GFAP induction by LPS in the dentate gyrus, a brain area linked to adult neurogenesis.