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Título
In vitro aging promotes endoplasmic reticulum (ER)-mitochondria Ca2 + cross talk and loss of store-operated Ca2 + entry (SOCE) in rat hippocampal neurons
Año del Documento
2016
Editorial
Elsevier
Descripción
Producción Científica
Documento Fuente
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2016, vol. 1863, n. 11. p. 2637-2649
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.
Palabras Clave
Aging
Envejecimiento
Hippocampal neurons
Neuronas hipocampales
Endoplasmic reticulum
Retículo endoplasmático
Mitochondria
Mitocondrias
ISSN
0167-4889
Revisión por pares
SI
Patrocinador
Ministerio de Economía, Industria y Competitividad (grants BFU2012-37146 and BFU2015-70131R)
Junta de Castilla y León (grants VA145U13 and BIO/VA33/13)
Junta de Castilla y León (grants VA145U13 and BIO/VA33/13)
Propietario de los Derechos
© 2016 Elsevier
Idioma
eng
Tipo de versión
info:eu-repo/semantics/publishedVersion
Derechos
openAccess
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