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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2017

Open Access 01-12-2017 | Research article

TRPA1 channels promote astrocytic Ca2+ hyperactivity and synaptic dysfunction mediated by oligomeric forms of amyloid-β peptide

Authors: Anthony Bosson, Adrien Paumier, Sylvie Boisseau, Muriel Jacquier-Sarlin, Alain Buisson, Mireille Albrieux

Published in: Molecular Neurodegeneration | Issue 1/2017

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Abstract

Background

Excessive synaptic loss is thought to be one of the earliest events in Alzheimer’s disease (AD). However, the key mechanisms that maintain plasticity of synapses during adulthood or initiate synapse dysfunction in AD remain unknown. Recent studies suggest that astrocytes contribute to functional changes observed during synaptic plasticity and play a major role in synaptic dysfunction but astrocytes behavior and involvement in early phases of AD remained largely undefined.

Methods

We measure astrocytic calcium activity in mouse CA1 hippocampus stratum radiatum in both the global astrocytic population and at a single cell level, focusing in the highly compartmentalized astrocytic arbor. Concurrently, we measure excitatory post-synaptic currents in nearby pyramidal neurons.

Results

We find that application of soluble Aβ oligomers (Aβo) induced fast and widespread calcium hyperactivity in the astrocytic population and in the microdomains of the astrocyte arbor. We show that astrocyte hyperactivity is independent of neuronal activity and is repaired by transient receptor potential A1 (TRPA1) channels blockade. In return, this TRPA1 channels-dependent hyperactivity influences neighboring CA1 neurons triggering an increase in glutamatergic spontaneous activity. Interestingly, in an AD mouse model (APP/PS1–21 mouse), astrocyte calcium hyperactivity equally takes place at the beginning of Aβ production, depends on TRPA1 channels and is linked to CA1 neurons hyperactivity.

Conclusions

Our experiments demonstrate that astrocytes contribute to early Aβo toxicity exhibiting a global and local Ca2+ hyperactivity that involves TRPA1 channels and is related to neuronal hyperactivity. Together, our data suggest that astrocyte is a frontline target of Aβo and highlight a novel mechanism for the understanding of early synaptic dysregulation induced by soluble Aβo species.
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Metadata
Title
TRPA1 channels promote astrocytic Ca2+ hyperactivity and synaptic dysfunction mediated by oligomeric forms of amyloid-β peptide
Authors
Anthony Bosson
Adrien Paumier
Sylvie Boisseau
Muriel Jacquier-Sarlin
Alain Buisson
Mireille Albrieux
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2017
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-017-0194-8

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