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dc.contributor.authorCacabelos Barral, Daniel
dc.contributor.authorRamírez-Núñez, Omar
dc.contributor.authorGranado-Serrano, Ana Belén
dc.contributor.authorTorres Cabestany, Pascual
dc.contributor.authorAyala Jové, Ma. Victoria (Maria Victoria)
dc.contributor.authorMoiseeva, Victoria
dc.contributor.authorPovedano, Mònica
dc.contributor.authorFerrer, Isidre
dc.contributor.authorPamplona Gras, Reinald
dc.contributor.authorPortero Otín, Manuel
dc.contributor.authorBoada Pallàs, Jordi
dc.description.abstractIntroduction: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with a gender bias towards major prevalence in male individuals. Several data suggest the involvement of oxidative stress and mitochondrial dysfunction in its pathogenesis, though differences between genders have not been evaluated. For this reason, we analysed features of mitochondrial oxidative metabolism, as well as mitochondrial chain complex enzyme activities and protein expression, lipid profile, and protein oxidative stress markers, in the Cu,Zn superoxide dismutase with the G93A mutation (hSOD1-G93A)- transgenic mice and Neuro2A(N2A) cells overexpressing hSOD1-G93A. Results and Conclusions: Our results show that overexpression of hSOD1-G93A in transgenic mice decreased efficiency of mitochondrial oxidative phosphorylation, located at complex I, revealing a temporal delay in females with respect to males associated with a parallel increase in selected markers of protein oxidative damage. Further, females exhibit a fatty acid profile with higher levels of docosahexaenoic acid at 30 days. Mechanistic studies showed that hSOD1-G93A overexpression in N2A cells reduced complex I function, a defect prevented by 17β- estradiol pretreatment. In conclusion, ALS-associated SOD1 mutation leads to delayed mitochondrial dysfunction in female mice in comparison with males, in part attributable to the higher oestrogen levels of the former. This study is important in the effort to further understanding of whether different degrees of spinal cord mitochondrial dysfunction could be disease modifiers in ALS. Keywords: Motor neuron, Complex I, Respirometry, Fatty acid composition, Oxidative damage, Estrogensca_ES
dc.description.sponsorshipThis study was funded by the Spanish Ministry of Health, Institute Carlos III: FIS grants PI14/00757, PI14/00328, PI 14/01115. Financed by the European Union, program European Regional Development Fund “A way to build Europe”. Supported by the Generalitat de Catalunya (2014SGR168 and predoctoral fellows for OR-N and PT), by FUNDELA (C100013), “RedELA Investigación” platform and by the Fundació Miquel Valls (Jack Van den Hoek donation for ALS research)ca_ES
dc.publisherBioMed Centralca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofActa Neuropathologica Communications, 2016, vol.4, núm. 3, p. 1-14ca_ES
dc.rightscc-by (c) Cacabelos, Daniel et al., 2016ca_ES
dc.subjectMotor neuronca_ES
dc.subjectComplex Ica_ES
dc.subjectFatty acid compositionca_ES
dc.titleEarly and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALSca_ES

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cc-by (c) Cacabelos, Daniel et al., 2016
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