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Title: Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer's disease
Authors: Calvo-Rodriguez, Maria
Hou, Steven S.
Snyder, Austin C.
Kharitonova, Elizabeth K.
Russ, Alyssa N.
Das, Sudeshna
Fan, Zhanyun
Muzikansky, Alona
Garcia-Alloza, Monica
Serrano-Pozo, Alberto
Hudry, Eloise
Bacskai, Brian J.
metadata.dc.contributor.authoraffiliation: [Calvo-Rodriguez,M; Hou,SS; Snyder,AC; Kharitonova,EK; Russ,AN; Das,S; Fan,Z; Serrano-Pozo,A; Hudry,E; Bacskai,BJ] Department of Neurology, Massachusetts General Hospital and Harvard Medical School, MA, USA. [Muzikansky,A] Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA. [Garcia-Alloza,M] Division of Physiology, School of Medicine, Instituto de Investigacion Biomedica de Cadiz (INIBICA), Universidad de Cadiz, Cadiz, Spain.
Keywords: Mitochondria;Calcium;Cell death;Amyloid;Brain;Genes;Microscopy;Alzheimer disease;Lead;Mitocondrias;Calcio;Muerte celular;Amiloide;Encéfalo;Microscopía;Enfermedad de Alzheimer;Plomo
metadata.dc.subject.mesh: Medical Subject Headings::Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Molecular Probe Techniques::Blotting, Western
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain
Medical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Elements::Metals, Alkaline Earth::Calcium
Medical Subject Headings::Anatomy::Cells::Cells, Cultured
Medical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytosol
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunohistochemistry
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Membrane Potentials::Membrane Potential, Mitochondrial
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BL
Medical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Mitochondria
Medical Subject Headings::Diseases::Nervous System Diseases::Neurodegenerative Diseases
Medical Subject Headings::Anatomy::Nervous System::Neurons
Issue Date: 1-May-2020
Publisher: Springer Nature
Citation: Calvo-Rodriguez M, Hou SS, Snyder AC, Kharitonova EK, Russ AN, Das S, et al. Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer's disease. Nat Commun. 2020 May 1;11(1):2146.
Abstract: Mitochondria contribute to shape intraneuronal Ca2+ signals. Excessive Ca2+ taken up by mitochondria could lead to cell death. Amyloid beta (Aβ) causes cytosolic Ca2+ overload, but the effects of Aβ on mitochondrial Ca2+ levels in Alzheimer's disease (AD) remain unclear. Using a ratiometric Ca2+ indicator targeted to neuronal mitochondria and intravital multiphoton microscopy, we find increased mitochondrial Ca2+ levels associated with plaque deposition and neuronal death in a transgenic mouse model of cerebral β-amyloidosis. Naturally secreted soluble Aβ applied onto the healthy brain increases Ca2+ concentration in mitochondria, which is prevented by blockage of the mitochondrial calcium uniporter. RNA-sequencing from post-mortem AD human brains shows downregulation in the expression of mitochondrial influx Ca2+ transporter genes, but upregulation in the genes related to mitochondrial Ca2+ efflux pathways, suggesting a counteracting effect to avoid Ca2+ overload. We propose lowering neuronal mitochondrial Ca2+ by inhibiting the mitochondrial Ca2+ uniporter as a novel potential therapeutic target against AD.
metadata.dc.identifier.doi: 10.1038/s41467-020-16074-2
ISSN: 2041-1723 (Online)
Appears in Collections:01 - Artículos - INiBICA. Instituto de Investigación e Innovación Biomédica de Cádiz

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