Sustained hippocampal IL-1beta overexpression impairs contextual and spatial memory in transgenic mice

Brain Behav Immun. 2010 Feb;24(2):243-53. doi: 10.1016/j.bbi.2009.10.002. Epub 2009 Oct 13.


Neuroinflammatory conditions such as traumatic brain injury, aging, Alzheimer's disease, and Down syndrome are often associated with cognitive dysfunction. Much research has targeted inflammation as a causative mediator of these deficits, although the diverse cellular and molecular changes that accompany these disorders obscure the link between inflammation and impaired memory. Therefore, we used a transgenic mouse model with a dormant human IL-1beta excisional activation transgene to direct overexpression of IL-1beta with temporal and regional control. Two weeks of hippocampal IL-1beta overexpression impaired long-term contextual and spatial memory in both male and female mice, while hippocampal-independent and short-term memory remained intact. Human IL-1beta overexpression activated glia, elevated murine IL-1beta protein and PGE(2) levels, and increased pro-inflammatory cytokine and chemokine mRNAs specifically within the hippocampus, while having no detectable effect on inflammatory mRNAs in the liver. Sustained neuroinflammation also reduced basal and conditioning-induced levels of the plasticity-related gene Arc.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Conditioning, Psychological
  • Cytoskeletal Proteins / metabolism
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Dinoprostone / biosynthesis
  • Fear / psychology
  • Female
  • Hippocampus / metabolism*
  • Hippocampus / physiology*
  • Humans
  • Immunodeficiency Virus, Feline / immunology
  • Immunohistochemistry
  • Interleukin-1beta / biosynthesis*
  • Interleukin-1beta / genetics
  • Male
  • Maze Learning / physiology
  • Mental Recall / physiology*
  • Mice
  • Mice, Transgenic
  • Microinjections
  • Nerve Tissue Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sex Characteristics
  • Space Perception / physiology*
  • Viral Vaccines / immunology


  • Cytoskeletal Proteins
  • DNA, Complementary
  • Interleukin-1beta
  • Nerve Tissue Proteins
  • Viral Vaccines
  • activity regulated cytoskeletal-associated protein
  • Dinoprostone