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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

IL-1β suppresses cLTP-induced surface expression of GluA1 and actin polymerization via ceramide-mediated Src activation

Authors: Liqi Tong, G. Aleph Prieto, Carl W. Cotman

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

Background

Brain inflammation including increases in inflammatory cytokines such as IL-1β is widely believed to contribute to the pathophysiology of Alzheimer’s disease. Although IL-1β-induced impairments in long-term potentiation (LTP) in acute hippocampal slices and memory functions in vivo have been well documented, the neuron-specific molecular mechanisms of IL-1β-mediated impairments of LTP and memory remain unclear.

Methods

This study uses an in vitro approach in primary hippocampal neurons to evaluate the effect of IL-1β on chemical LTP (cLTP)-induced structural plasticity and signaling.

Results

We found that IL-1β reduces both the surface expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA1 and the spine growth following cLTP. These effects of IL-1β were mediated by impairing actin polymerization during cLTP, as IL-1β decreased the cLTP-induced formation of F-actin, and the effect of IL-1β on cLTP-induced surface expression of GluA1 can be mimicked by latrunculin, a toxin that disrupts dynamics of actin filaments, and can be prevented by jasplakinolide, a cell-permeable peptide that stabilizes F-actin. Moreover, live-cell imaging demonstrated that IL-1β decreased the stability of the actin cytoskeleton in spines, which is required for LTP consolidation. We further examined the role of sphingolipid signaling in the IL-1β-mediated impairment of spine plasticity and found that both the neutral sphingomyelinase inhibitor GW4869 and the inhibitor of Src kinase PP2 attenuated the IL-1β-mediated suppression of cLTP-induced surface expression of GluA1 and actin polymerization.

Conclusions

These findings support a mechanism by which IL-1β, via the sphingomyelinase/ceramide/Src pathway, impairs structural spine remodeling essential for LTP consolidation and memory.
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Metadata
Title
IL-1β suppresses cLTP-induced surface expression of GluA1 and actin polymerization via ceramide-mediated Src activation
Authors
Liqi Tong
G. Aleph Prieto
Carl W. Cotman
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1158-9

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