English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/188479
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:


The APPswe/PS1A246E mutations in an astrocytic cell line leads to increased vulnerability to oxygen and glucose deprivation, Ca2+ dysregulation, and mitochondrial abnormalities

AuthorsMartin-de-Saavedra, María; Navarro, Elisa; Moreno-Ortega, Ana J.; Cunha, Mauricio P.; Buendía Abaitua, Izaskun; Hernansanz-Agustín, Pablo; León Martínez, Rafael; Cano-Abad, María F.; Martínez-Ruiz, Antonio ; Martínez-Murillo, Ricardo ; Duchen, Michael R.; López, Manuela G.
KeywordsAlzheimer's disease
Calcium dyshomeostasis
Cell death
Mitochondrial dysfunction
Issue Date2018
PublisherInternational Society for Neurochemistry
John Wiley & Sons
CitationJournal of Neurochemistry 145(2): 170-182 (2018)
AbstractGrowing evidence suggests a close relationship between Alzheimer's Disease (AD) and cerebral hypoxia. Astrocytes play a key role in brain homeostasis and disease states, while some of the earliest changes in AD occur in astrocytes. We have therefore investigated whether mutations associated with AD increase astrocyte vulnerability to ischemia. Two astroglioma cell lines derived from APPSWE /PS1A246E (APP, amyloid precursor protein; PS1, presenilin 1) transgenic mice and controls from normal mice were subjected to oxygen and glucose deprivation (OGD), an in vitro model of ischemia. Cell death was increased in the APPSWE /PS1A246E line compared to the control. Increasing extracellular calcium concentration ([Ca2+ ]) exacerbated cell death in the mutant but not in the control cells. In order to explore cellular Ca2+ homeostasis, the cells were challenged with ATP or thapsigargin and [Ca2+ ] was measured by fluorescence microscopy. Changes in cytosolic Ca2+ concentration ([Ca2+ ]c ) were potentiated in the APPSWE /PS1A246E transgenic line. Mitochondrial function was also altered in the APPSWE /PS1A246E astroglioma cells; mitochondrial membrane potential and production of reactive oxygen species were increased, while mitochondrial basal respiratory rate and ATP production were decreased compared to control astroglioma cells. These results suggest that AD mutations in astrocytes make them more sensitive to ischemia; Ca2+ dysregulation and mitochondrial dysfunction may contribute to this increased vulnerability. Our results also highlight the role of astrocyte dyshomeostasis in the pathophysiology of neurodegenerative brain disorders.
Publisher version (URL)https://doi.org/10.1111/jnc.14293
Appears in Collections:(IIBM) Artículos
(IC) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf59,24 kBAdobe PDFThumbnail
Show full item record
Review this work

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.