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dc.contributor.authorBeyer, Marianna M S
dc.contributor.authorLonnemann, Niklas
dc.contributor.authorRemus, Anita
dc.contributor.authorLatz, Eicke
dc.contributor.authorHeneka, Michael T
dc.contributor.authorKorte, Martin
dc.date.accessioned2020-08-03T10:47:40Z
dc.date.available2020-08-03T10:47:40Z
dc.date.issued2020-06-04
dc.identifier.citationJ Neurosci. 2020;40(28):5480-5494. doi:10.1523/JNEUROSCI.0200-20.2020.en_US
dc.identifier.pmid32499379
dc.identifier.doi10.1523/JNEUROSCI.0200-20.2020
dc.identifier.urihttp://hdl.handle.net/10033/622375
dc.description.abstractNeuroinflammation can be caused by various insults to the brain and represents an important pathologic hallmark of neurodegenerative diseases including Alzheimer's disease (AD). Infection-triggered acute systemic inflammation is able to induce neuroinflammation and may negatively affect neuronal morphology, synaptic plasticity, and cognitive function. In contrast to acute effects, persisting consequences for the brain on systemic immune stimulation remain largely unexplored. Here, we report an age-dependent vulnerability of wild-type (WT) mice of either sex toward a systemic immune stimulation by Salmonella typhimurium lipopolysaccharide (LPS). Decreased neuronal complexity three months after peripheral immune stimulation is accompanied by impairment in long-term potentiation (LTP) and spatial learning. Aged APP/PS1 mice reveal an increased sensitivity also to LPS of Escherichia coli, which had no effect in WT mice. We further report that these effects are mediated by NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation, since the genetic ablation and pharmacological inhibition using the NLRP3 inhibitor MCC950 rescue the morphological and electrophysiological phenotype.SIGNIFICANCE STATEMENT Acute peripheral immune stimulation has been shown to have both positive and negative effects on Aβ deposition. Improvements or worsening may be possible in acute inflammation. However, there is still no evidence of effects longer than a month after stimulation. The data are pointing to an important role of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome for mediating the long-term consequences of systemic immune stimulation, which in addition turns out to be age dependent.en_US
dc.language.isoenen_US
dc.publisherSociety for Neuroscienceen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectAPP/PS1en_US
dc.subjectLPSen_US
dc.subjectNLRP3en_US
dc.subjecthippocampusen_US
dc.subjectneuroinflammationen_US
dc.subjectsepsisen_US
dc.titleEnduring Changes in Neuronal Function upon Systemic Inflammation Are NLRP3 Inflammasome Dependent.en_US
dc.typeArticleen_US
dc.identifier.eissn1529-2401
dc.identifier.journalThe Journal of neuroscience : the official journal of the Society for Neuroscienceen_US
dc.source.volume40
dc.source.issue28
dc.source.beginpage5480
dc.source.endpage5494
dc.source.journaltitleThe Journal of neuroscience : the official journal of the Society for Neuroscience
dc.source.countryUnited States


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Attribution-NonCommercial-ShareAlike 4.0 International
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