Succinate increases neuronal post-synaptic excitatory potentials in vitro and induces convulsive behavior through N-methyl-D-aspartate-mediated mechanisms

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dc.contributor.authorRoehrs, C.
dc.contributor.authorGarrido-Sanabria, E. R.
dc.contributor.authorDa Silva, A. C.
dc.contributor.authorFaria, L. C.
dc.contributor.authorSinhorin, VDG
dc.contributor.authorMarques, R. H.
dc.contributor.authorPriel, M. R.
dc.contributor.authorRubin, M. A.
dc.contributor.authorCavalheiro, E. A.
dc.contributor.authorMello, C. F.
dc.contributor.institutionUniversidade Federal de Sergipe (UFS)
dc.contributor.institutionUniv Texas
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T12:34:12Z
dc.date.available2016-01-24T12:34:12Z
dc.date.issued2004-01-01
dc.description.abstractSuccinate is a dicarboxylic acid that accumulates due to succinate dehydrogenase inhibition by malonate and methylmalonate exposure. These neurotoxins cause increased excitability and excitotoxic damage, which can be prevented by administering high amounts of succinate. in the present study we investigated whether succinate alters hippocampal field excitatory post-synaptic potentials. Bath application of succinate at intermediate concentrations (0.31 mM) increased the slope of field excitatory post-synaptic potentials in hippocampal slices, and at high concentrations (above 1 mM) did not alter or decrease field excitatory postsynaptic potentials slope. Succinate-induced enhancement of field excitatory post-synaptic potentials slope was abolished by the addition of D-2-amino-5-phosphonovaleric acid (50 muM) to the perfusate, supporting the involvement of N-methyl-D-aspartate receptors in the excitatory effect of this organic acid. Accordingly, succinate (0.8-7.5 mumol) i.c.v. administration caused dose-dependent convulsive behavior in mice. the i.c.v. co-administration of MK-801 (7 nmol) fully prevented succinate-induced convulsions, further suggesting the involvement of N-methyl-D-aspartate receptors in the convulsant action of succinate. Our data indicate that accumulation of moderate amounts of succinate may contribute to the excitotoxicity induced by succinate dehydrogenase inhibitors, through the activation of N-methyl-D-aspartate receptors. (C) 2004 IBRO. Published by Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Fed Santa Maria, Dept Physiol, BR-97105900 Santa Maria, RS, Brazil
dc.description.affiliationUniv Texas, Dept Biol, Brownville, TX USA
dc.description.affiliationUniversidade Federal de São Paulo, Lab Expt Neurol, BR-04023900 São Paulo, Brazil
dc.description.affiliationFed Univ Santa Maria, Dept Chem, BR-97105900 Santa Maria, RS, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Lab Expt Neurol, BR-04023900 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent965-971
dc.identifierhttp://dx.doi.org/10.1016/j.neuroscience.2004.01.058
dc.identifier.citationNeuroscience. Oxford: Pergamon-Elsevier B.V., v. 125, n. 4, p. 965-971, 2004.
dc.identifier.doi10.1016/j.neuroscience.2004.01.058
dc.identifier.issn0306-4522
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/27545
dc.identifier.wosWOS:000221679300014
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofNeuroscience
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectsuccinateen
dc.subjectconvulsionen
dc.subjectfield excitatory post-synaptic potentialsen
dc.subjectsuccinate dehydrogenaseen
dc.subjectmethylmalonic acidemiaen
dc.subjectmalonic acidemiaen
dc.titleSuccinate increases neuronal post-synaptic excitatory potentials in vitro and induces convulsive behavior through N-methyl-D-aspartate-mediated mechanismsen
dc.typeinfo:eu-repo/semantics/article
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