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The astrocyte as a frontline target in the toxicity phenomena induced by the amyloid-beta peptide

on the July 7, 2017
Research, Biology - Medecine - Health

Early involvement of astrocytes in the synaptic dysfunction associated with Alzheimer's disease

The loss of synapses is a major event of Alzheimer's disease responsible for the memory and cognitive decline characteristic of the disease. The presence of soluble oligomers of the amyloid-beta (Abeta) peptide in the brain is determinant in this early synaptic loss. Recent studies suggest that astrocytes can play a major role in synaptic plasticity process, learning and memory, but also in synaptic dysfunction. Indeed, astrocytes interact extremely dynamically with neurons. In particular, their finest extensions enwrap synapses and thus modulate synaptic transmission. This communication between astrocytes and neurons is bilateral and involves calcium signals at the astrocytic level that combine with neuronal electrical signals. The team "Neuropathologies and Synaptic Dysfunctions" of the Grenoble Institute of Neurosciences studied the dynamics of these astrocytic calcium signals in the fine processes of astrocytes and demonstrated a major effect of the amyloid-beta peptide on this signaling which affects neighboring synaptic activity. This study was published in the journal Molecular Neurodegeneration in July 2017.

Alain Buisson's team is developing a project to characterize the cellular and molecular mechanisms underlying early Alzheimer's disease by focusing on the synapse as the primary target of the disease. The astrocyte is a major partner of the synapse and its involvement in the early phenomena of synaptotoxicity is one of the axes developed by the team. Thus, interactions between neurons and astrocytes have been studied within the brain hippocampus of healthy mice and Alzheimer's disease models. The researchers found that astrocytic calcium signaling was strongly disrupted in the presence of the Abeta peptide with the emergence of localized calcium hyperactivity at the level of astrocytes territory. This hyperactivity is both extremely compartmentalized in the fine processes of the astrocyte and also present in the whole astrocytic network. This local and global hyperactivity is due to the activation of a particular astrocytic calcium channel, the TRPA1 channel. The blockade of this channel is sufficient to restore a basal astrocytic calcium activity but above all is sufficient to stop the perturbations of the synaptic transmission which result from the presence of the Abeta peptide. This involvement of the astrocyte is extremely fast, i.e. occuring from the first minutes of the presence of Abeta at the extracellular level. Thus, the astrocyte can be considered as a particularly early target in the toxicity of Abeta with consequent impairment of neighboring synaptic transmission. The beneficial or deleterious role played by TRPA1 in this astrocytic calcium hyperactivity is at the center of the current research of the team.

Calcium activity is analyzed in the whole astrocytic territory from mouse hippocampus. 


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

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

Molecular Neurodegeneration (2017) 12 (53) : 1-19

DOI 10.1186/s13024-017-0194-8

Updated on December 8, 2017

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