Influence of N-methyl-D-aspartate receptors on ouabain activation of nuclear factor-κB in the rat hippocampus
Version of Record online: 18 OCT 2011
Copyright © 2011 Wiley Periodicals, Inc.
Journal of Neuroscience Research
Volume 90, Issue 1, pages 213–228, January 2012
How to Cite
Kawamoto, E.M., Lima, L.S., Munhoz, C.D., Yshii, L.M., Kinoshita, P.F., Amara, F.G., Pestana, R.R.F., Orellana, A.M.M., Cipolla-Neto, J., Britto, L.R.G., Avellar, M.C.W., Rossoni, L.V. and Scavone, C. (2012), Influence of N-methyl-D-aspartate receptors on ouabain activation of nuclear factor-κB in the rat hippocampus. J. Neurosci. Res., 90: 213–228. doi: 10.1002/jnr.22745
- Issue online: 15 NOV 2011
- Version of Record online: 18 OCT 2011
- Manuscript Accepted: 27 JUN 2011
- Manuscript Revised: 25 JUN 2011
- Manuscript Received: 28 DEC 2010
- Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP. Grant Number: 2003/08989-0
- Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq. Grant Number: 485953-2007-2
It has been shown that ouabain (OUA) can activate the Na,K-ATPase complex and mediate intracellular signaling in the central nervous system (CNS). Inflammatory stimulus increases glutamatergic transmission, especially at N-methyl-D-aspartate (NMDA) receptors, which are usually coupled to the activation of nitric oxide synthase (NOS). Nuclear factor-κB (NF-κB) activation modulates the expression of genes involved in development, plasticity, and inflammation. The present work investigated the effects of OUA on NF-κB binding activity in rat hippocampus and the influence of this OUA-Na,K-ATPase signaling cascade in NMDA-mediated NF-κB activation. The findings presented here are the first report indicating that intrahippocampal administration of OUA, in a concentration that did not alter Na,K-ATPase or NOS activity, induced an activation of NF-κB, leading to increases in brain-derived neurotrophic factor (Bdnf), inducible NOS (iNos), tumor necrosis factor-α (Tnf-α), and B-cell leukemia/lymphoma 2 (Bcl2) mRNA levels. This response was not linked to any significant signs of neurodegeneration as showed via Fluoro-Jade B and Nissl stain. Intrahippocampal administration of NMDA induced NF-κB activation and increased NOS and α2/3-Na,K-ATPase activities. NMDA treatment further increased OUA-induced NF-κB activation, which was partially blocked by MK-801, an antagonist of NMDA receptor. These results suggest that OUA-induced NF-κB activation is at least in part dependent on Na,K-ATPase modulatory action of NMDA receptor in hippocampus. The interaction of these signaling pathways could be associated with biological mechanisms that may underlie the basal homeostatic state linked to the inflammatory signaling cascade in the brain. © 2011 Wiley Periodicals, Inc.