title: Effects of Aluminium on Rat Brain Mitochondria Bioenergetics: an In vitro and In vivo Study.
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.
authors.affiliation: Laboratory of Neurochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.|The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Javier
authors.initials: J
authors.lastname: Iglesias-González
authors.affiliation: Laboratory of Neurochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Sofía
authors.initials: S
authors.lastname: Sánchez-Iglesias
authors.affiliation: Laboratory of Histology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Beiras-Iglesias
authors.affiliation: Laboratory of Neurochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.|Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Méndez-Álvarez
authors.affiliation: Laboratory of Neurochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain. ramon.soto@usc.es.|Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain. ramon.soto@usc.es.
authors.forename: Ramón
authors.initials: R
authors.lastname: Soto-Otero
mesh_terms: D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000535:Aluminum
keywords: Aluminium; High-resolution respirometry; Mitochondria; Oxidative stress; Parkinson’s disease; Rat brain