Impaired interleukin-1beta and c-Fos expression in the hippocampus is associated with a spatial memory deficit in P2X(7) receptor-deficient mice

PLoS One. 2009 Jun 23;4(6):e6006. doi: 10.1371/journal.pone.0006006.


Recent evidence suggests that interleukin-1beta (IL-1beta), which was originally identified as a proinflammatory cytokine, is also required in the brain for memory processes. We have previously shown that IL-1beta synthesis in the hippocampus is dependent on P2X(7) receptor (P2X(7)R), which is an ionotropic receptor of ATP. To substantiate the role of P2X(7)R in both brain IL-1beta expression and memory processes, we examined the induction of IL-1beta mRNA expression in the hippocampus of wild-type (WT) and homozygous P2X(7) receptor knockout mice (P2X(7)R(-/-)) following a spatial memory task. The spatial recognition task induced both IL-1beta mRNA expression and c-Fos protein activation in the hippocampus of WT but not of P2X(7)R(-/-) mice. Remarkably, P2X(7)R(-/-) mice displayed spatial memory impairment in a hippocampal-dependant task, while their performances in an object recognition task were unaltered. Taken together, our results show that P2X(7)R plays a critical role in spatial memory processes and the associated hippocampal IL-1beta mRNA synthesis and c-Fos activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Brain / metabolism
  • Hippocampus / metabolism*
  • Interleukin-1beta / biosynthesis*
  • Interleukin-1beta / metabolism
  • Maze Learning / physiology
  • Memory
  • Memory Disorders / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Receptors, Purinergic P2 / genetics*
  • Receptors, Purinergic P2 / physiology
  • Receptors, Purinergic P2X7
  • Reverse Transcriptase Polymerase Chain Reaction


  • Interleukin-1beta
  • P2rx7 protein, mouse
  • Proto-Oncogene Proteins c-fos
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7