Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Neurobiol Aging. 2012 Mar;33(3):603-616.e3. doi: 10.1016/j.neurobiolaging.2010.04.002. Epub 2010 May 14.

Systemic inflammation induces acute working memory deficits in the primed brain: relevance for delirium.

Author information

  • 1Trinity College Institute of Neuroscience, School of Biochemistry & Immunology, Trinity College Dublin, Dublin, Ireland.

Abstract

Delirium is an acute, severe neuropsychiatric syndrome, characterized by cognitive deficits, that is highly prevalent in aging and dementia and is frequently precipitated by peripheral infections. Delirium is poorly understood and the lack of biologically relevant animal models has limited basic research. Here we hypothesized that synaptic loss and accompanying microglial priming during chronic neurodegeneration in the ME7 mouse model of prion disease predisposes these animals to acute dysfunction in the region of prior pathology upon systemic inflammatory activation. Lipopolysaccharide (LPS; 100 μg/kg) induced acute and transient working memory deficits in ME7 animals on a novel T-maze task, but did not do so in normal animals. LPS-treated ME7 animals showed heightened and prolonged transcription of inflammatory mediators in the central nervous system (CNS), compared with LPS-treated normal animals, despite having equivalent levels of circulating cytokines. The demonstration that prior synaptic loss and microglial priming are predisposing factors for acute cognitive impairments induced by systemic inflammation suggests an important animal model with which to study aspects of delirium during dementia.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
20471138
[PubMed - indexed for MEDLINE]
PMCID:
PMC3200140
Free PMC Article

Images from this publication.See all images (7)Free text

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Figure S1
Figure S2
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk