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Effects of Aluminium on Rat Brain Mitochondria Bioenergetics: an In vitro and In vivo Study

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Abstract

Numerous studies have highlighted the potential of aluminium as an aetiological factor for some neurodegenerative disorders, particularly Alzheimer’s disease and Parkinson’s disease. Our previous studies have shown that aluminium can cause oxidative stress, reduce the activity of some antioxidant enzymes, and enhance the dopaminergic neurodegeneration induced by 6-hydroxydopamine in an experimental model of Parkinson’s disease in rats. We now report a study on the effects caused by aluminium on mitochondrial bioenergetics following aluminium addition and after its chronic administration to rats. To develop our study, we used a high-resolution respirometry to test the mitochondrial respiratory capacities under the conditions of coupling, uncoupling, and non-coupling. Our study showed alterations in leakiness, a reduction in the maximum capacity of complex II-linked respiratory pathway, a decline in the respiration efficiency, and a decrease in the activities of complexes III and V in both models studied. The observed effects also included both an alteration in mitochondrial transmembrane potential and a decrease in oxidative phosphorylation capacity when relatively high concentrations of aluminium were added to the isolated mitochondria. These findings contribute to explain both the ability of aluminium to generate oxidative stress and its suggested potential to act as an etiological factor by promoting the progression of neurodegenerative disorders such as Parkinson’s disease.

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Abbreviations

Al3+ :

Aluminium

ANT:

Adenine nucleotide translocator

CI:

Complex I

CII:

Complex II

E:

Uncoupled state

ETS:

Electron transport system

ETSmax :

Non-coupled respiration

FCCP:

Carbonyl cyanide-4-(trifluoromethoxy)-phenylhydrazone

L:

Resting state after ATP synthase inhibition

mPTP:

Mitochondrial permeability transition pore

OXPHOS:

Oxidative phosphorylation

P:

ADP activated state

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

SUIT:

Substrate-uncoupler-inhibitor-titration

TCA:

Tricarboxylic acid cycle

TTP+ :

Tetraphenylphosphonium

Δψ:

Mitochondria transmembrane potential

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Acknowledgments

This study was financially supported by grant 09CSA005298PR from the Galician Government (XUGA), Santiago de Compostela, Spain.

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Author notes

  1. Javier Iglesias-González

    Present address: The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK

Authors and Affiliations

  1. Laboratory of Neurochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain

    Javier Iglesias-González, Sofía Sánchez-Iglesias, Estefanía Méndez-Álvarez & Ramón Soto-Otero

  2. Laboratory of Histology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain

    Andrés Beiras-Iglesias

  3. Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain

    Estefanía Méndez-Álvarez & Ramón Soto-Otero

Authors
  1. Javier Iglesias-González
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  2. Sofía Sánchez-Iglesias
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Correspondence to Ramón Soto-Otero.

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Iglesias-González, J., Sánchez-Iglesias, S., Beiras-Iglesias, A. et al. Effects of Aluminium on Rat Brain Mitochondria Bioenergetics: an In vitro and In vivo Study. Mol Neurobiol 54, 563–570 (2017). https://doi.org/10.1007/s12035-015-9650-z

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  • DOI: https://doi.org/10.1007/s12035-015-9650-z

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