Impact of blunting astrocyte activity on hippocampal synaptic plasticity in a mouse model of early Alzheimer's disease based on amyloid‐β peptide exposure
- 19 January 2022
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 160 (5), 556-567
- https://doi.org/10.1111/jnc.15575
Abstract
Amyloid-β peptides (Aβ) accumulate in the brain since early Alzheimer’s disease (AD) and dysregulate hippocampal synaptic plasticity, the neurophysiological basis of memory. Although the relationship between long-term potentiation (LTP) and memory processes is well established, there is also evidence that long-term depression (LTD) may be crucial for learning and memory. Alterations in synaptic plasticity, namely in LTP, can be due to communication failures between astrocytes and neurons; however, little is known about astrocytes´ ability to control hippocampal LTD, particularly in AD-like conditions. We now aimed to test the involvement of astrocytes in changes of hippocampal LTP and LTD triggered by Aβ1-42, taking advantage of L-α-aminoadipate (L-AA), a gliotoxin that blunts astrocytic function. The effects of Aβ1-42 exposure was tested in two different experimental paradigms: ex vivo (hippocampal slices superfusion) and in vivo (intracerebroventricular injection), which were previously validated to impair memory and hippocampal synaptic plasticity, two features of early AD. Blunting astrocytic function with L-AA reduced LTP and LTD amplitude in hippocampal slices from control mice but the effect on LTD was less evident, suggesting that astrocytes have a greater influence on LTP than on LTD under non-pathological conditions. However, under AD conditions, blunting astrocytes did not consistently alter the reduction of LTP magnitude and reverted the LTD-to-LTP shift caused by both ex vivo and in vivo Aβ1-42 exposure. This shows that astrocytes were responsible for the hippocampal LTD-to-LTP shift observed in early AD conditions, reinforcing the interest of strategies targeting astrocytes to restore memory and synaptic plasticity deficits present in early AD.Keywords
Funding Information
- Fundação para a Ciência e a Tecnologia (PTDC/MED‐NEU/31274/2017; UIDB/04539/2020)
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