RT info:eu-repo/semantics/article
T1 Aging and amyloid β oligomers enhance TLR4 expression, LPS-induced Ca2+ responses, and neuron cell death in cultured rat hippocampal neurons
A1 Calvo Rodríguez, María
A1 Fuente, Carmen de la
A1 García Durillo, Mónica
A1 García Rodríguez, Carmen
A1 Villalobos Jorge, Carlos
A1 Núñez Llorente, Lucía
K1 Aging
K1 Envejecimiento
K1 Toll-like receptor 4
K1 Receptor 4 tipo Toll
K1 Alzheimer’s disease
K1 Enfermedad de Alzheimer
K1 Hippocampal neurons
K1 Neuronas hipocampales
K1 Calcium
K1 Calcio
AB Background: Toll-like receptors (TLRs) are transmembrane pattern-recognition receptors of the innate immune system recognizing diverse pathogen-derived and tissue damage-related ligands. It has been suggested that TLR signaling contributes to the pathogenesis of age-related, neurodegenerative diseases, including Alzheimer’s disease (AD). AD is associated to oligomers of the amyloid β peptide (Aβo) that cause intracellular Ca2+ dishomeostasis and neuron cell death in rat hippocampal neurons. Here we assessed the interplay between inflammation and Aβo in long-term cultures of rat hippocampal neurons, an in vitro model of neuron aging and/or senescence. Methods: Ca2+ imaging and immunofluorescence against annexin V and TLR4 were applied in short- and long-term cultures of rat hippocampal neurons to test the effects of TLR4-agonist LPS and Aβo on cytosolic [Ca2+] and on apoptosis as well as on expression of TLR4. Results: LPS increases cytosolic [Ca2+] and promotes apoptosis in rat hippocampal neurons in long-term culture considered aged and/or senescent neurons, but not in short-term cultured neurons considered young neurons. TLR4 antagonist CAY10614 prevents both effects. TLR4 expression in rat hippocampal neurons is significantly larger in aged hippocampal cultures. Treatment of aged hippocampal cultures with Aβo increases TLR4 expression and enhances LPS-induced Ca2+ responses and neuron cell death. Conclusions: Aging and amyloid β oligomers, the neurotoxin involved in Alzheimer’s disease, enhance TLR4 expression as well as LPS-induced Ca2+ responses and neuron cell death in rat hippocampal neurons aged in vitro.
PB BioMed Central
SN 1742-2094
YR 2017
FD 2017
LK http://uvadoc.uva.es/handle/10324/45036
UL http://uvadoc.uva.es/handle/10324/45036
LA eng
NO Journal of Neuroinflammation, 2017, vol. 14. 13 p.
NO Producción Científica
DS UVaDOC
RD 22-dic-2024