%0 Journal Article
%A Calvo-Rodriguez, Maria
%A Hou, Steven S.
%A Snyder, Austin C.
%A Kharitonova, Elizabeth K.
%A Russ, Alyssa N.
%A Das, Sudeshna
%A Fan, Zhanyun
%A Muzikansky, Alona
%A Garcia-Alloza, Monica
%A Serrano-Pozo, Alberto
%A Hudry, Eloise
%A Bacskai, Brian J.
%T Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer's disease
%D 2020
%U http://hdl.handle.net/10668/3567
%X 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.
%K Mitochondria
%K Calcium
%K Cell death
%K Amyloid
%K Brain
%K Genes
%K Microscopy
%K Alzheimer disease
%K Lead
%K Mitocondrias
%K Calcio
%K Muerte celular
%K Amiloide
%K Encéfalo
%K Microscopía
%K Enfermedad de Alzheimer
%K Plomo
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