Aging and Amyloid β Oligomers Enhance TLR4 Expression, LPS-induced Ca Responses, and Neuron Cell Death in Cultured Rat Hippocampal Neurons

Overview

Journal J Neuroinflammation

Publisher Biomed Central

Date 2017 Feb 2

PMID 28143556

Citations 55

Authors

Maria Calvo-Rodriguez

Carmen de la Fuente

Monica Garcia-Durillo

Carmen Garcia-Rodriguez

Carlos Villalobos

Lucia Nunez

Affiliations

Soon will be listed here.

Abstract

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 Ca 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: Ca 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 [Ca] and on apoptosis as well as on expression of TLR4.

Results: LPS increases cytosolic [Ca] 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 Ca 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 Ca responses and neuron cell death in rat hippocampal neurons aged in vitro.

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