Intrastriatal methylmalonic acid administration induces convulsions and TBARS production, and alters Na+,K+-ATPase activity in the rat striatum and cerebral cortex

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dc.contributor.authorMalfatti, CRM
dc.contributor.authorRoyes, LFF
dc.contributor.authorFrancescato, L.
dc.contributor.authorSanabria, Emilio Rafael Garrido [UNIFESP]
dc.contributor.authorRubin, M. A.
dc.contributor.authorCavalheiro, Esper Abrão [UNIFESP]
dc.contributor.authorMello, C. F.
dc.contributor.institutionUniversidade Federal de Sergipe (UFS)
dc.contributor.institutionUniv Santa Cruz Do Sul
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T12:33:51Z
dc.date.available2016-01-24T12:33:51Z
dc.date.issued2003-06-01
dc.description.abstractPurpose: Methylmalonic acid (MMA) inhibits succinate dehydrogenase (SDH) and beta-hydroxybutyrate dehydrogenase activity in vitro. Acute intrastriatal administration of MMA induces convulsions through glutamatergic mechanisms probably involving primary adenosine triphosphate (ATP) depletion and free radical generation. in this study we investigated whether the intrastriatal administration of MMA causes lipoperoxidation and alteration in Na+, K+-ATPase activity ex vivo and characterized the electrographic changes elicited by the intrastriatal administration of this organic acid.Methods: MMA-induced lipoperoxidation, alterations in Na+, K+-ATPase activity and electrographic changes were measured by measuring total thiobarbituric acid-reacting substances and inorganic phosphate release by spectrophotometry, and by depth electrode recording, respectively.Results: We demonstrated that intrastriatal NIMA (6 mmol) injection causes convulsive behavior and electrographically recorded convulsions that last similar to2 h. Concomitant with the increase of thiobarbituric acid-reacting substances (TBARS) content, we observed a significant inhibition of Na+,K+-ATPase activity in the striatum, and activation of Na+K+-ATPase activity in the ipsilateral cerebral cortex. Intrastriatal MMA injection increased the content of TBARS in the striatum measured 30 min (32.4 +/- 12.0%, compared with the noninjected contralateral striatum) and 3 h (39.7 +/- 5.1%, compared with the noninjected contralateral striatum) after MMA injection. TBARS content of the ipsilateral cerebral cortex increased after MMA injection at 30 min (42.1 +/- 6.0%) and 3 h (40.4 +/- 20.2%), and Na+K+-TPase activity in the ipsilateral cerebral cortex increased during ictal activity (113.8 +/- 18%) and returned to basal levels as electrographic convulsions vanished in the cortex. Interestingly, intrastriatal MMA administration induced a persistent decrease in Na+K+-ATPase activity only in the injected striatum (44.9 +/- 8.1 % at 30 min and 68.7 +/- 9.4 at 3 h).Conclusions: These data suggest that MMA induces lipoperoxidation associated with Na+,K+-ATPase inhibition or activation, depending on the cerebral structure analyzed. It is suggested that Na+,K+-ATPase inhibition may play a primary role in generating MMA-induced convulsions.en
dc.description.affiliationUniv Fed Santa Maria, Dept Quim, BR-97105900 Santa Maria, RS, Brazil
dc.description.affiliationUniv Santa Cruz Do Sul, Santa Cruz Do Sul, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Lab Neurol Expt, Cruz Alta, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Lab Neurol Expt, Cruz Alta, Brazil
dc.description.sourceWeb of Science
dc.format.extent761-767
dc.identifierhttp://dx.doi.org/10.1046/j.1528-1157.2003.42902.x
dc.identifier.citationEpilepsia. Malden: Blackwell Publishing Inc, v. 44, n. 6, p. 761-767, 2003.
dc.identifier.doi10.1046/j.1528-1157.2003.42902.x
dc.identifier.issn0013-9580
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/27259
dc.identifier.wosWOS:000183840300003
dc.language.isoeng
dc.publisherBlackwell Publishing Inc
dc.relation.ispartofEpilepsia
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectNa+,K+-ATPaseen
dc.subjectTBARSen
dc.subjectmethylmalonic academiaen
dc.subjectmethylmalonateen
dc.subjectconvulsionen
dc.subjectEEGen
dc.subjectstriatumen
dc.subjectcortexen
dc.subjectraten
dc.titleIntrastriatal methylmalonic acid administration induces convulsions and TBARS production, and alters Na+,K+-ATPase activity in the rat striatum and cerebral cortexen
dc.typeinfo:eu-repo/semantics/article
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