title: Endogenous IL-1 in cognitive function and anxiety: a study in IL-1RI-/- mice.
abstract: Interleukin-1 (IL-1) is a key pro-inflammatory cytokine, produced predominantly by peripheral immune cells but also by glia and some neuronal populations within the brain. Its signalling is mediated via the binding of IL-1α or IL-1β to the interleukin-1 type one receptor (IL-1RI). IL-1 plays a key role in inflammation-induced sickness behaviour, resulting in depressed locomotor activity, decreased exploration, reduced food and water intake and acute cognitive deficits. Conversely, IL-1 has also been suggested to facilitate hippocampal-dependent learning and memory: IL-1RI(-/-) mice have been reported to show deficits on tasks of visuospatial learning and memory. We sought to investigate whether there is a generalised hippocampal deficit in IL-1RI(-/-) animals. Therefore, in the current study we compared wildtype (WT) mice to IL-1RI(-/-) mice using a variety of hippocampal-dependent learning and memory tasks, as well as tests of anxiety and locomotor activity. We found no difference in performance of the IL-1RI(-/-) mice compared to WT mice in a T-maze working memory task. In addition, the IL-1RI(-/-) mice showed normal learning in various spatial reference memory tasks including the Y-maze and Morris mater maze, although there was a subtle deficit in choice behaviour in a spatial discrimination, beacon watermaze task. IL-1RI(-/-) mice also showed normal memory for visuospatial context in the contextual fear conditioning paradigm. In the open field, IL-1RI(-/-) mice showed a significant increase in distance travelled and rearing behaviour compared to the WT mice and in the elevated plus-maze spent more time in the open arms than did the WT animals. The data suggest that, contrary to prior studies, IL-1RI(-/-) mice are not robustly impaired on hippocampal-dependent memory and learning but do display open field hyperactivity and decreased anxiety compared to WT mice. The results argue for a careful evaluation of the roles of endogenous IL-1 in hippocampal and limbic system function.
authors.affiliation: School of Biochemistry and Immunology & Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Republic of Ireland.
authors.forename: Carol L
authors.initials: CL
authors.lastname: Murray
authors.forename: Pauline
authors.initials: P
authors.lastname: Obiang
authors.forename: David
authors.initials: D
authors.lastname: Bannerman
authors.forename: Colm
authors.initials: C
authors.lastname: Cunningham
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001008:Anxiety Disorders / Q000378:metabolism*; D003071:Cognition / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology; D005239:Fear / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D055809:Illness Behavior / Q000502:physiology; D007375:Interleukin-1 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism*
chemical_list: C583355:IL1R1 protein, mouse; D007375:Interleukin-1; D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I