Astrocytic IL-6 mediates locomotor activity, exploration, anxiety, learning and social behavior

• Published in: Hormones and behavior 2015-07, Vol.73, p.64-74
• Main Authors: Erta, Maria, Giralt, Mercedes, Esposito, Flavia Lorena, Fernandez-Gayol, Olaya, Hidalgo, Juan
• Format: Article
• Language: English
• Subjects: Animal behavior; Animals; Anxiety; Anxiety - genetics; Anxiety - metabolism; Anxiety - physiopathology; Astrocyte; Astrocytes - metabolism; Behavior, Animal; Brain; Cells; Cytokines; Elevated plus-maze; Exploratory Behavior; Hippocampus - metabolism; Hole-board; IL-6; Interleukin-6 - genetics; Interleukin-6 - metabolism; Interleukin-6 - physiology; Intrauterine survival; Learning - physiology; Male; Maze Learning - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Morris water-maze; Motor Activity - genetics; Rodents; Social Behavior; Spatial learning; Transgenic mice
• ISSN: 0018-506X; 1095-6867
• DOI: 10.1016/j.yhbeh.2015.06.016

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. [Display omitted] •IL-6 produced by astrocytes controls behavior.•Astrocytes themselves but also other brain cells influence behavior in response to IL-6.•Activity, anxiety and spatial learning are the most sensitive behavioral traits influenced by IL-6.•No evidence of changes in the basal activity of the hypothalamus–pituitary–adrenal axis of these transgenic mice