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Title

In vitro ageing and Alzheimer's disease related amyloid oligomers enhance Ca2+ responses and neuron cell death induced by the Toll-like receptor ligand lipopolysaccharide

AuthorsNúñez, Lucía ; Calvo-Rodríguez, María; Fuente, Carmen de la; García-Durillo, Mónica; García-Rodríguez, Carmen ; Villalobos, Carlos
Issue Date2017
Citation7th Workshop of the European Calcium Society (2017)
AbstractToll-like receptors (TLRs) are a family of innate immune system receptors involved in sensing and responding to pathogen-associated molecular patterns (PAMPs) and endogenous ligands known as damage-associated molecular patterns (DAMPs) released upon cell damage and necrosis. TLR4 is the receptor for lipopolysaccharide (LPS) present in Gram-negative bacteria and it is widely expressed in a diversity of mammalian immune and non-immune cells including brain cells. lt has been proposed that TLR4 may contribute to neural plasticity and development in neurons. In addition, TLR4 expression is upregulated with normal aging suggesting involvement in agerelated neurodegenerative disorders such as Alzheimer's disease (AD). AD, the most common form of dementia characterized by the gradualloss of memory and cognitive function, is strongly associated to aging. The causes for AD are still not well understood. AD is associated to formation of amyloid plaques made up of amyloid β peptide (Aβ), mainly Aβ 1-42. We have shown that Aβ oligomers, the most likely toxin in Alzheimer's disease, may promete neuron cell death acting on intracellular Ca2+ homeostasis. The tlr4 gene has emerged as a candidate susceptibility gene for AD. However, the possible interactions of LPS and Aβ on hippocampal neurons have not been assessed yet. In this work, we aimed at investigating the interplay between neuroinflammation and AD in the context of aging. To accomplish the above goal, we have employed long-term cultures of rat hippocampal neurons, which are considered a model of agin and/or senescence, and investigate the effects of LPS and/or Aβ oligomers on Ca2+ levels and neuron cell death. Our results show that rat hippocampal neurons express TLR4 and expression increases with time in culture consistently with in vivo aging. We also found that LPS increases cytosolic [Ca2+] and prometes neuron cell death only in aged cultures. Treatment with AD-related oligomers of the amyloid β peptide (Aβo) further enhanced TLR4 expression as well as Ca2+ responses induced by LPS and neuron cell death, suggesting the interplay between TLR4 and Aβo in neuron cell death associated to aging and AD.
DescriptionResumen del trabajo presentado al 7th Workshop of the European Calcium Society (ECS), celebrado en toulouse (Francia) del 16 al 18 de octubre de 2017.
URIhttp://hdl.handle.net/10261/197719
Appears in Collections:(IBGM) Comunicaciones congresos
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