Treatment with the glutamate modulator riluzole prevents early life stress-induced cognitive deficits and impairments in synaptic plasticity in APPswe/PS1dE9 mice

Neuropharmacology
Sylvie L LesuisHarm J Krugers

Abstract

Environmental factors like stress affect age-related cognitive deficits and promote Alzheimer's disease (AD)-related pathology in mice. Excess glutamate has been proposed as a possible mediator underlying these effects in the hippocampus, a vulnerable brain region implicated in learning and memory. Here, we examined a) whether stress applied during a sensitive developmental period early in life affects later synaptic plasticity, learning and memory and plaque load in the APPswe/PS1dE9 mouse model for Alzheimer's disease and b) whether these effects could be rescued using long-term treatment with the glutamate modulator riluzole. Our results demonstrate that ELS impairs synaptic plasticity in 6-month-old mice and increases plaque load in 12-month-old APPswe/PS1dE9 mice, while impairing flexible spatial learning in the Barnes maze at this age. Notably, spatial learning correlated well with hippocampal expression of the transporter EAAT2, which is important for extracellular glutamate uptake. The changes in LTP, plaque load and cognition after ELS were all prevented by riluzole treatment that started from post-weaning. These results suggest that normalising glutamate signalling may be a viable therapeutic strategy for treating vul...Continue Reading

Citations

Sep 26, 2019·Frontiers in Pharmacology·Alessandra CarusoSergio Scaccianoce
Mar 22, 2020·Journal of Neuroinflammation·Maralinde R AbbinkAniko Korosi
Mar 8, 2020·Journal of Alzheimer's Disease : JAD·Masafumi Ihara, Satoshi Saito
Oct 28, 2020·Journal of Neurochemistry·Kevin N HascupErin R Hascup
Aug 15, 2021·The European Journal of Neuroscience·Amanda L WrightAdam K Walker
Dec 12, 2021·Nature Reviews. Neuroscience·Gerard SanacoraMaurizio Popoli

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