Glutamate-induced alterations in Ca2+ signaling are modulated by mitochondrial Ca2+ handling capacity in brain slices of R6/1 transgenic mice

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dc.contributor.authorRosenstock, T. R. [UNIFESP]
dc.contributor.authorBertoncini, C. R. A. [UNIFESP]
dc.contributor.authorTeles, A. V. [UNIFESP]
dc.contributor.authorHirata, H. [UNIFESP]
dc.contributor.authorFernandes, M. J. S. [UNIFESP]
dc.contributor.authorSmaili, Soraya Soubhi [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:05:10Z
dc.date.available2016-01-24T14:05:10Z
dc.date.issued2010-07-01
dc.description.abstractHuntington's disease is a neurodegenerative disorder caused by an expansion of CAGs repeats and characterized by alterations in mitochondrial functions. Although changes in Ca2+ handling have been suggested, the mechanisms involved are not completely understood. the aim of this study was to investigate the possible alterations in Ca2+ handling capacity and the relationship with mitochondrial dysfunction evaluated by NAD(P)H fluorescence, reactive oxygen species levels, mitochondrial membrane potential (Delta Psi(m)) measurements and respiration in whole brain slices from R6/1 mice of different ages, evaluated in situ by real-time real-space microscopy. We show that the cortex and striatum of the 9-month-old R6/1 transgenic mice present a significant sustained increase in cytosolic Ca2+ induced by glutamate (Glu). This difference in Glu response was partially reduced in R6/1 when in the absence of extracellular Ca2+, indicating that N-methyl-d-aspartate receptors participation in this response is more important in transgenic mice. in addition, Glu also lead to a decrease in NAD(P)H fluorescence, a loss in Delta Psi(m) and a further increase in respiration, which may have evoked a decrease in mitochondrial Ca2+ (Ca-m(2+)) uptake capacity. Taken together, these results show that alterations in Ca2+ homeostasis in transgenic mice are associated with a decrease in Ca-m(2+) uptake mechanism with a diminished Ca2+ handling ability that ultimately causes dysfunctions and worsening of the neurodegenerative and the disease processes.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Farmacol, EPM, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Ctr Desenvolvimento Modelos Animais Med & Biol CE, EPM, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Neurol & Neurocirurgia, EPM, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Farmacol, EPM, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Ctr Desenvolvimento Modelos Animais Med & Biol CE, EPM, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Neurol & Neurocirurgia, EPM, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent60-70
dc.identifierhttp://dx.doi.org/10.1111/j.1460-9568.2010.07268.x
dc.identifier.citationEuropean Journal of Neuroscience. Malden: Wiley-Blackwell, v. 32, n. 1, p. 60-70, 2010.
dc.identifier.doi10.1111/j.1460-9568.2010.07268.x
dc.identifier.issn0953-816X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32704
dc.identifier.wosWOS:000279612400008
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofEuropean Journal of Neuroscience
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectcalciumen
dc.subjectexcitotoxicityen
dc.subjectHuntington's diseaseen
dc.subjectmitochondriaen
dc.subjectR6/1 miceen
dc.titleGlutamate-induced alterations in Ca2+ signaling are modulated by mitochondrial Ca2+ handling capacity in brain slices of R6/1 transgenic miceen
dc.typeinfo:eu-repo/semantics/article
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