title: In vitro aging promotes endoplasmic reticulum (ER)-mitochondria Ca2+cross talk and loss of store-operated Ca2+entry (SOCE) in rat hippocampal neurons.
abstract: Aging is associated to cognitive decline and susceptibility to neuron death, two processes related recently to subcellular Ca2+homeostasis. Memory storage relies on mushroom spines stability that depends on store-operated Ca2+entry (SOCE). In addition, Ca2+transfer from endoplasmic reticulum (ER) to mitochondria sustains energy production but mitochondrial Ca2+overload promotes apoptosis. We have addressed whether SOCE and ER-mitochondria Ca2+transfer are influenced by culture time in long-term cultures of rat hippocampal neurons, a model of neuronal aging. We found that short-term cultured neurons show large SOCE, low Ca2+store content and no functional coupling between ER and mitochondria. In contrast, in long-term cultures reflecting aging neurons, SOCE is essentially lost, Stim1 and Orai1 are downregulated, Ca2+stores become overloaded, Ca2+release is enhanced, expression of the mitochondrial Ca2+uniporter (MCU) increases and most Ca2+released from the ER is transferred to mitochondria. These results suggest that neuronal aging is associated to increased ER-mitochondrial cross talking and loss of SOCE. This subcellular Ca2+remodeling might contribute to cognitive decline and susceptibility to neuron cell death in the elderly.
authors: Instituto de Biología y Genética Molecular (IBGM), Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain.
authors: María
authors: M
authors: Calvo-Rodríguez
authors: Instituto de Biología y Genética Molecular (IBGM), Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain.
authors: Mónica
authors: M
authors: García-Durillo
authors: Instituto de Biología y Genética Molecular (IBGM), Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain. Electronic address: carlosv@ibgm.uva.es.
authors: Carlos
authors: C
authors: Villalobos
authors: Instituto de Biología y Genética Molecular (IBGM), Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain; Departamento de Bioquímica y Biología Molecular y Fisiología, Universidad de Valladolid, Valladolid, Spain.
authors: Lucía
authors: L
authors: Núñez
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000071740:ORAI1 Protein / Q000378:metabolism*; D017208:Rats, Wistar; D000071737:Stromal Interaction Molecule 1 / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; C532493:Orai1 protein, rat; C518857:Stim1 protein, rat; D000071737:Stromal Interaction Molecule 1; C034703:mitochondrial calcium uniporter; D002110:Caffeine; D000109:Acetylcholine
keywords: Aging; ER-mitochondria cross talking; Hippocampal neurons; Orai1; Stim1; Store-operated calcium entry