Back to Search
Start Over
Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer's disease
- Source :
- Nature Communications (2020) 11:2146, RODIN. Repositorio de Objetos de Docencia e Investigación de la Universidad de Cádiz, instname, RODIN: Repositorio de Objetos de Docencia e Investigación de la Universidad de Cádiz, Universidad de Cádiz, Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020)
- Publication Year :
- 2020
- Publisher :
- NATURE PUBLISHING GROUP, 2020.
-
Abstract
- Mitochondria contribute to shape intraneuronal Ca2+ signals. Excessive Ca2+ taken up by mitochondria could lead to cell death. Amyloid beta (A beta) causes cytosolic Ca2+ overload, but the effects of A beta 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 beta -amyloidosis. Naturally secreted soluble A beta 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. Calvo-Rodriguez et al. show elevated calcium levels in neuronal mitochondria in a mouse model of cerebral beta -amyloidosis after plaque deposition, which precede rare neuron death events in this model. The mechanism involves toxic extracellular A beta oligomers and the mitochondrial calcium uniporter.
- Subjects :
- 0301 basic medicine
Male
Plomo
General Physics and Astronomy
Mitochondrion
Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunohistochemistry [Medical Subject Headings]
Mice
0302 clinical medicine
Cytosol
Microscopía
Enfermedad de Alzheimer
Organisms::Eukaryota::Animals [Medical Subject Headings]
lcsh:Science
Anatomy::Nervous System::Neurons [Medical Subject Headings]
Cells, Cultured
Mitocondrias
Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Mitochondria [Medical Subject Headings]
Membrane Potential, Mitochondrial
Neurons
Microscopy
Multidisciplinary
biology
Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Molecular Probe Techniques::Blotting, Western [Medical Subject Headings]
Brain
Neurodegenerative Diseases
Immunohistochemistry
Cell biology
Mitochondria
Chemicals and Drugs::Inorganic Chemicals::Elements::Metals, Alkaline Earth::Calcium [Medical Subject Headings]
Encéfalo
Alzheimer disease
Neuron death
Genetically modified mouse
Cell death
Programmed cell death
Amyloid
Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease [Medical Subject Headings]
Amyloid beta
Science
Blotting, Western
chemistry.chemical_element
Check Tags::Male [Medical Subject Headings]
Calcium
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Calcio
Diseases::Nervous System Diseases::Neurodegenerative Diseases [Medical Subject Headings]
Animals
Uniporter
Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytosol [Medical Subject Headings]
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings]
Amiloide
Phenomena and Processes::Cell Physiological Phenomena::Membrane Potentials::Membrane Potential, Mitochondrial [Medical Subject Headings]
General Chemistry
Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings]
Muerte celular
Mice, Inbred C57BL
030104 developmental biology
chemistry
Genes
Lead
Anatomy::Cells::Cells, Cultured [Medical Subject Headings]
biology.protein
lcsh:Q
Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BL [Medical Subject Headings]
030217 neurology & neurosurgery
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Nature Communications (2020) 11:2146, RODIN. Repositorio de Objetos de Docencia e Investigación de la Universidad de Cádiz, instname, RODIN: Repositorio de Objetos de Docencia e Investigación de la Universidad de Cádiz, Universidad de Cádiz, Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020)
- Accession number :
- edsair.doi.dedup.....e26b55b79ff36c7a4f5e2e60b93236be