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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2014

Open Access 01-12-2014 | Research

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

Authors: Paula Fernanda Kinoshita, Lidia Mitiko Yshii, Andrea Rodrigues Vasconcelos, Ana Maria Marques Orellana, Larissa de Sá Lima, Ana Paula Couto Davel, Luciana Venturini Rossoni, Elisa Mitiko Kawamoto, Cristoforo Scavone

Published in: Journal of Neuroinflammation | Issue 1/2014

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.
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Metadata
Title
Signaling function of Na,K-ATPase induced by ouabain against LPS as an inflammation model in hippocampus
Authors
Paula Fernanda Kinoshita
Lidia Mitiko Yshii
Andrea Rodrigues Vasconcelos
Ana Maria Marques Orellana
Larissa de Sá Lima
Ana Paula Couto Davel
Luciana Venturini Rossoni
Elisa Mitiko Kawamoto
Cristoforo Scavone
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2014
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-014-0218-z

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