Impaired interleukin-1beta and c-Fos expression in the hippocampus is associated with a spatial memory deficit in P2X(7) receptor-deficient mice.
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.
Labrousse
Virginie F
VF
Psychoneuroimmunologie, Nutrition et Génétique (PsyNuGen), INRA UMR 1286, CNRS UMR 5226, Université de Bordeaux, Bordeaux, France.
Costes
Laurence
L
Aubert
Agnès
A
Darnaudéry
Muriel
M
Ferreira
Guillaume
G
Amédée
Thierry
T
Layé
Sophie
S
D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D008568:Memory; D008569:Memory Disorders / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000502:physiology; D058486:Receptors, Purinergic P2X7; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053583:Interleukin-1beta; C546469:P2rx7 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7