Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS

Introduction: 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 ev...

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Authors: Cacabelos, Daniel, Ramírez Núñez, Omar, Granado Serrano, Ana Belén, Torres, Pascual, Ayala, Victòria, Moiseeva, Victoria, Povedano, Mònica, Ferrer, Isidro (Ferrer Abizanda), Pamplona, Reinald, Portero-Otin, Manuel, Boada, Jordi
Format: article
Status:Published version
Publication Date:2016
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/127048
Online Access:https://hdl.handle.net/2445/127048
Access Level:Open access
Keyword:Malalties neuromusculars
Esclerosi lateral amiotròfica
Factors sexuals en les malalties
Neuromuscular diseases
Amyotrophic lateral sclerosis
Sex factors in disease
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spelling Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALSCacabelos, DanielRamírez Núñez, OmarGranado Serrano, Ana BelénTorres, PascualAyala, VictòriaMoiseeva, VictoriaPovedano, MònicaFerrer, Isidro (Ferrer Abizanda)Pamplona, ReinaldPortero-Otin, ManuelBoada, JordiMalalties neuromuscularsEsclerosi lateral amiotròficaFactors sexuals en les malaltiesNeuromuscular diseasesAmyotrophic lateral sclerosisSex factors in diseaseIntroduction: 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 17βestradiol 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.BioMed Central2018201820162018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/2445/127048Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1186/s40478-015-0271-6Acta Neuropathologica Communications, 2016, vol. 4, p. 3https://doi.org/10.1186/s40478-015-0271-6cc-by (c) Cacabelos, Daniel et al., 2016http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1270482026-05-29T05:05:01Z
dc.title.none.fl_str_mv Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS
title Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS
spellingShingle Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS
Cacabelos, Daniel
Malalties neuromusculars
Esclerosi lateral amiotròfica
Factors sexuals en les malalties
Neuromuscular diseases
Amyotrophic lateral sclerosis
Sex factors in disease
title_short Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS
title_full Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS
title_fullStr Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS
title_full_unstemmed Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS
title_sort Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS
dc.creator.none.fl_str_mv Cacabelos, Daniel
Ramírez Núñez, Omar
Granado Serrano, Ana Belén
Torres, Pascual
Ayala, Victòria
Moiseeva, Victoria
Povedano, Mònica
Ferrer, Isidro (Ferrer Abizanda)
Pamplona, Reinald
Portero-Otin, Manuel
Boada, Jordi
author Cacabelos, Daniel
author_facet Cacabelos, Daniel
Ramírez Núñez, Omar
Granado Serrano, Ana Belén
Torres, Pascual
Ayala, Victòria
Moiseeva, Victoria
Povedano, Mònica
Ferrer, Isidro (Ferrer Abizanda)
Pamplona, Reinald
Portero-Otin, Manuel
Boada, Jordi
author_role author
author2 Ramírez Núñez, Omar
Granado Serrano, Ana Belén
Torres, Pascual
Ayala, Victòria
Moiseeva, Victoria
Povedano, Mònica
Ferrer, Isidro (Ferrer Abizanda)
Pamplona, Reinald
Portero-Otin, Manuel
Boada, Jordi
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malalties neuromusculars
Esclerosi lateral amiotròfica
Factors sexuals en les malalties
Neuromuscular diseases
Amyotrophic lateral sclerosis
Sex factors in disease
topic Malalties neuromusculars
Esclerosi lateral amiotròfica
Factors sexuals en les malalties
Neuromuscular diseases
Amyotrophic lateral sclerosis
Sex factors in disease
description Introduction: 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 17βestradiol 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.
publishDate 2016
dc.date.none.fl_str_mv 2016
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/127048
url https://hdl.handle.net/2445/127048
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s40478-015-0271-6
Acta Neuropathologica Communications, 2016, vol. 4, p. 3
https://doi.org/10.1186/s40478-015-0271-6
dc.rights.none.fl_str_mv cc-by (c) Cacabelos, Daniel et al., 2016
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Cacabelos, Daniel et al., 2016
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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