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

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

Author Rosenstock, T. R. Autor UNIFESP Google Scholar
Bertoncini, C. R. A. Autor UNIFESP Google Scholar
Teles, A. V. Autor UNIFESP Google Scholar
Hirata, H. Autor UNIFESP Google Scholar
Fernandes, M. J. S. Autor UNIFESP Google Scholar
Smaili, Soraya Soubhi Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Huntington'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.
Keywords calcium
excitotoxicity
Huntington's disease
mitochondria
R6/1 mice
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2010-07-01
Published in European Journal of Neuroscience. Malden: Wiley-Blackwell, v. 32, n. 1, p. 60-70, 2010.
ISSN 0953-816X (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 60-70
Origin http://dx.doi.org/10.1111/j.1460-9568.2010.07268.x
Access rights Closed access
Type Article
Web of Science ID WOS:000279612400008
URI http://repositorio.unifesp.br/handle/11600/32704

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