Systemic Inflammation Induces Acute Working Memory Deficits in the Primed Brain: Relevance for Delirium

Neurobiol Aging. 2012 Mar;33(3):603-616.e3. doi: 10.1016/j.neurobiolaging.2010.04.002. Epub 2010 May 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Delirium / pathology
  • Delirium / physiopathology
  • Dementia / pathology
  • Dementia / physiopathology
  • Disease Models, Animal
  • Female
  • Inflammation / complications
  • Inflammation / pathology
  • Inflammation Mediators / administration & dosage
  • Lipopolysaccharides / administration & dosage
  • Memory Disorders / pathology*
  • Memory Disorders / physiopathology
  • Memory, Short-Term / physiology*
  • Mice
  • Mice, Inbred C57BL

Substances

  • Inflammation Mediators
  • Lipopolysaccharides