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Alzheimer et PGE2: des relations enflammées

La voie de signalisation PGE2-EP3 altère la plasticité synaptique dans l'hippocampe d'un modèle de souris "Alzheimer"

Le 13 décembre 2016

PGE2-EP3 signaling pathway impairs hippocampal presynaptic long-term plasticity in a mouse model of Alzheimer’s disease.  Maingret V, Barthet G, Deforges S, Jiang N, Mulle C, Amédée T. Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France; University of Bordeaux, Bordeaux, France. Neurobiol Aging. 2016 Oct 17;50:13-24. doi: 10.1016/j.neurobiolaging.2016.10.012. [Epub ahead of print]

Team "Synaptic Circuits of Memory" teamleader:  Christophe Mulle



Abstract / Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by early cognitive deficits linked to synaptic dysfunction and loss. Considerable evidence suggests that neuroinflammation contributes to AD. Prostaglandin E2 (PGE2), a key neuroinflammatory molecule, modulates hippocampal synaptic transmission and plasticity. We investigated the effect of PGE2 on synaptic transmission and presynaptic plasticity at synapses between mossy fibers from the dentate gyrus and CA3 pyramidal cells (Mf-CA3 synapse). These synapses are involved in mnemonic processes and consequently may be of relevance for AD. We provide evidence that although PGE2 had no effect both on either basal transmission or short-term plasticity, it strongly impaired presynaptic Mf-CA3 long-term potentiation (LTP) by acting on PGE2 receptor 3 (EP3) receptors. During aging, hippocampal levels of PGE2 markedly increased in the APP/PS1 mouse model of AD and impaired specifically presynaptic LTP via a PGE2-EP3 signaling pathway. In summary, the building up of PGE2 during the progression of AD leads to specific impairment of hippocampal presynaptic plasticity and highlights EP3 receptors as a potential target to alleviate cognitive deficits in AD

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Thierry Amédée / Research Director at the CNRS / Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France; University of Bordeaux, Bordeaux, France.
Dernière mise à jour le 13.12.2016