title: PGE2-EP3 signaling pathway impairs hippocampal presynaptic long-term plasticity in a mouse model of Alzheimer's disease.
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 PGE2on 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 PGE2had no effect both on either basal transmission or short-term plasticity, it strongly impaired presynaptic Mf-CA3 long-term potentiation (LTP) by acting on PGE2receptor 3 (EP3) receptors. During aging, hippocampal levels of PGE2markedly 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 PGE2during 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.
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France; University of Bordeaux, Bordeaux, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Maingret
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France; University of Bordeaux, Bordeaux, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Barthet
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France; University of Bordeaux, Bordeaux, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Deforges
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France; University of Bordeaux, Bordeaux, France.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France; University of Bordeaux, Bordeaux, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Mulle
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France; University of Bordeaux, Bordeaux, France. Electronic address: thierry.amedee@u-bordeaux.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Amédée
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000502:physiology*; D000544:Alzheimer Disease / Q000209:etiology* / Q000628:therapy; D000818:Animals; D015232:Dinoprostone / Q000502:physiology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000503:physiopathology*; D017774:Long-Term Potentiation; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D009473:Neuronal Plasticity / Q000235:genetics* / Q000502:physiology*; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics* / Q000502:physiology
chemical_list: C545647:PTGER3 protein, human; D058308:Receptors, Prostaglandin E, EP3 Subtype; D015232:Dinoprostone
keywords: APP/PS1; Alzheimer's disease; Hippocampus; Inflammation; PGE(2); Synaptic plasticity