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

Maria Erta, Mercedes Giralt, Flavia Lorena Esposito, Olaya Fernandez-Gayol, Juan Hidalgo*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

34 Citations (Scopus)


© 2015 Elsevier Inc. 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.
Original languageEnglish
Pages (from-to)64-74
JournalHormones and Behavior
Publication statusPublished - 1 Jul 2015


  • Anxiety
  • Astrocyte
  • Elevated plus-maze
  • Exploratory behavior
  • Hole-board
  • IL-6
  • Intrauterine survival
  • Morris water-maze
  • Spatial learning
  • Transgenic mice


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