PGE₂-EP3 signaling pathway impairs hippocampal presynaptic long-term plasticity in a mouse model of Alzheimer's disease

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• 作者：Vincent Maingret^a ; ^b ; Gaë ; l Barthet^a ; ^b ; Sé ; verine Deforges^a ; ^b ; Nan Jiang^a ; ^b ; Christophe Mulle^a ; ^b ; Thierry Amé ; dé ; e^a ; ^b ; ^{thierry.amedee@u-bordeaux.fr}
• 关键词：Alzheimer's disease ; Inflammation ; PGE2 ; Synaptic plasticity ; Hippocampus ; APP/PS1
• 刊名：Neurobiology of Aging
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：50
• 期：Complete
• 页码：13-24
• 全文大小：2259 K
• 卷排序：50

文摘

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.