PGE 2 -EP3 signaling pathway impairs hippocampal presynaptic long-term plasticity in a mouse model of Alzheimer's disease
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 E (PGE ), a key neuroinflammatory molecule, modulates hip...
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Published in | Neurobiology of aging Vol. 50; pp. 13 - 24 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.02.2017
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Subjects | |
Online Access | Get full text |
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Summary: | 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 E
(PGE
), a key neuroinflammatory molecule, modulates hippocampal synaptic transmission and plasticity. We investigated the effect of PGE
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 PGE
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 PGE
receptor 3 (EP3) receptors. During aging, hippocampal levels of PGE
markedly increased in the APP/PS1 mouse model of AD and impaired specifically presynaptic LTP via a PGE
-EP3 signaling pathway. In summary, the building up of PGE
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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ISSN: | 0197-4580 1558-1497 |
DOI: | 10.1016/j.neurobiolaging.2016.10.012 |