Prolonged elevation in hippocampal Aβ and cognitive deficits following repeated endotoxin exposure in the mouse

Behav Brain Res. 2012 Apr 1;229(1):176-84. doi: 10.1016/j.bbr.2012.01.010. Epub 2012 Jan 12.


Alzheimer's disease (AD) is characterized by neuronal cell death and atrophy in regions of the adult brain, including the hippocampus and cortex, due to formation of amyloid beta (Aβ) plaques and neurofibrillary tangles. The presence of these pathologies can limit normal signaling properties and ultimately lead to learning and memory deficits. Chronic inflammation has been implicated in the onset and progression of these AD-related pathologies. Our study was designed to assess the effects of peripheral inflammation on pathologies associated with AD by using the bacterial endotoxin lipopolysaccharide (LPS). C57BL/6J mice were given intraperitoneal injections of LPS or saline for 1, 3, or 7 consecutive days. Hippocampal tissue from animals receiving LPS contained significantly higher levels of Aβ1-42, a peptide component of AD plaques, than did those from saline control animals. Central and peripheral pro-inflammatory cytokine levels were increased following a single injection of LPS, but retuned to baseline levels before cognitive testing began. We show that one injection of LPS leads to sickness behavior, but 7 consecutive days does not, indicating tolerance to the endotoxin. Cognitive testing was then conducted to determine if whether deficits from increased Aβ1-42 was evident. Results from both Morris water maze and contextual fear conditioning revealed cognitive deficits in LPS-treated mice. In summary, multiple injections of LPS resulted in increased Aβ1-42 in the hippocampus and cognitive deficits in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Analysis of Variance
  • Animals
  • Cognition Disorders / blood
  • Cognition Disorders / chemically induced*
  • Conditioning, Psychological / drug effects
  • Drug Administration Schedule
  • Endotoxins / adverse effects*
  • Enzyme-Linked Immunosorbent Assay
  • Exploratory Behavior / drug effects
  • Fear / drug effects
  • Hippocampus / drug effects*
  • Hippocampus / metabolism*
  • Inflammation / chemically induced
  • Inflammation / complications
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interleukin-1beta / blood
  • Lipopolysaccharides / adverse effects*
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / metabolism*
  • Time Factors
  • Weight Loss / drug effects


  • Amyloid beta-Peptides
  • Endotoxins
  • Interleukin-1beta
  • Lipopolysaccharides
  • Peptide Fragments
  • amyloid beta-protein (1-42)