title: Astrocytic IL-6 mediates locomotor activity, exploration, anxiety, learning and social behavior.
abstract: Interleukin-6 (IL-6) is a major cytokine in the central nervous system, secreted by different brain cells and with roles in a number of physiological functions. We herewith confirm and expand the importance of astrocytic production of and response to IL-6 by using transgenic mice deficient in astrocytic IL-6 (Ast-IL-6 KO) or in its receptor (Ast-IL-6R KO) in full C57Bl/6 genetic background. A major prosurvival effect of astrocytic IL-6 at early ages was clearly demonstrated. Robust effects were also evident in the control of activity and anxiety in the hole-board and elevated plus-maze, and in spatial learning in the Morris water-maze. The results also suggest an inhibitory role of IL-6 in the mechanism controlling the consolidation of hippocampus-dependent spatial learning. Less robust effects of astrocytic IL-6 system were also observed in despair behavior in the tail suspension test, and social behavior in the dominance and resident-intruder tests. The behavioral phenotype was highly dependent on age and/or sex in some cases. The phenotype of Ast-IL-6R KO mice mimicked only partially that of Ast-IL-6KO mice, which indicates both a role of astrocytes in behavior and the participation of other cells besides astrocytes. No evidences of altered function of the hypothalamic-pituitary-adrenal axis were observed. These results demonstrate that astrocytic IL-6 (acting at least partially in astrocytes) regulates normal behavior in mice.
authors.affiliation: Institute of Neurosciences, and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain. Electronic address: mariaerta@gmail.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Erta
authors.affiliation: Institute of Neurosciences, and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain. Electronic address: merce.giralt@uab.es.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Giralt
authors.affiliation: Institute of Neurosciences, and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain. Electronic address: flavia-noa@hotmail.com.
authors.forename: Flavia Lorena
authors.initials: FL
authors.lastname: Esposito
authors.affiliation: Institute of Neurosciences, and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain. Electronic address: olaya.fernandez@uab.es.
authors.forename: Olaya
authors.initials: O
authors.lastname: Fernandez-Gayol
authors.affiliation: Institute of Neurosciences, and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain. Electronic address: Juan.Hidalgo@uab.es.
authors.forename: Juan
authors.initials: J
authors.lastname: Hidalgo
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001253:Astrocytes / Q000378:metabolism*; D001522:Behavior, Animal; D005106:Exploratory Behavior; D006624:Hippocampus / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics*; D012919:Social Behavior
chemical_list: D015850:Interleukin-6
keywords: Anxiety; Astrocyte; Elevated plus-maze; Exploratory behavior; Hole-board; IL-6; Intrauterine survival; Morris water-maze; Spatial learning; Transgenic mice