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Influence of N-methyl-D-aspartate receptors on ouabain activation of nuclear factor-κB in the rat hippocampus.
J Neurosci Res. 2012 Jan; 90(1):213-28.JN

Abstract

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 α(2/3) -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.

Authors+Show Affiliations

Molecular Neuropharmacology Laboratory, Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22006678

Citation

Kawamoto, E M., et al. "Influence of N-methyl-D-aspartate Receptors On Ouabain Activation of Nuclear factor-κB in the Rat Hippocampus." Journal of Neuroscience Research, vol. 90, no. 1, 2012, pp. 213-28.
Kawamoto EM, Lima LS, Munhoz CD, et al. Influence of N-methyl-D-aspartate receptors on ouabain activation of nuclear factor-κB in the rat hippocampus. J Neurosci Res. 2012;90(1):213-28.
Kawamoto, E. M., Lima, L. S., Munhoz, C. D., Yshii, L. M., Kinoshita, P. F., Amara, F. G., Pestana, R. R., Orellana, A. M., Cipolla-Neto, J., Britto, L. R., Avellar, M. C., Rossoni, L. V., & Scavone, C. (2012). Influence of N-methyl-D-aspartate receptors on ouabain activation of nuclear factor-κB in the rat hippocampus. Journal of Neuroscience Research, 90(1), 213-28. https://doi.org/10.1002/jnr.22745
Kawamoto EM, et al. Influence of N-methyl-D-aspartate Receptors On Ouabain Activation of Nuclear factor-κB in the Rat Hippocampus. J Neurosci Res. 2012;90(1):213-28. PubMed PMID: 22006678.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of N-methyl-D-aspartate receptors on ouabain activation of nuclear factor-κB in the rat hippocampus. AU - Kawamoto,E M, AU - Lima,L S, AU - Munhoz,C D, AU - Yshii,L M, AU - Kinoshita,P F, AU - Amara,F G, AU - Pestana,R R F, AU - Orellana,A M M, AU - Cipolla-Neto,J, AU - Britto,L R G, AU - Avellar,M C W, AU - Rossoni,L V, AU - Scavone,C, Y1 - 2011/10/18/ PY - 2010/12/28/received PY - 2011/06/25/revised PY - 2011/06/27/accepted PY - 2011/10/19/entrez PY - 2011/10/19/pubmed PY - 2012/3/14/medline SP - 213 EP - 28 JF - Journal of neuroscience research JO - J Neurosci Res VL - 90 IS - 1 N2 - 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 α(2/3) -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. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/22006678/Influence_of_N_methyl_D_aspartate_receptors_on_ouabain_activation_of_nuclear_factor_κB_in_the_rat_hippocampus_ L2 - https://doi.org/10.1002/jnr.22745 DB - PRIME DP - Unbound Medicine ER -