Prolonged Restraint Stress Increases IL-6, Reduces IL-10, and Causes Persistent Depressive-Like Behavior That Is Reversed by Recombinant IL-10

PLoS One

Andrew J. Tarr¹  John F. Sheridan²  Clay B. Marsh³  Eric S. Wohleb⁴  Xiaokui Mo⁴  Timothy D. Eubank⁵  Jonathan P. Godbout⁵  Jeffrey L. Voorhees⁶ 

[1] Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America;Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, United States of America;Department of Neuroscience, The Ohio State University, Columbus, Ohio, United States of America;Division of Oral Biology, The Ohio State University, Columbus, Ohio, United States of America;Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, United States of America;The Dorothy M. Davis Heart and Lung Research Institute, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, Ohio, United States of America

关键词: Depression;    Psychological stress;    Cytokines;    Animal behavior;    Mice;    Behavior;    Hippocampus;    Swimming;   

DOI  :  10.1371/journal.pone.0058488

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Altered inflammatory cytokine profiles are often observed in individuals suffering from major depression. Recent clinical work reports on elevated IL-6 and decreased IL-10 in depression. Elevated IL-6 has served as a consistent biomarker of depression and IL-10 is proposed to influence depressive behavior through its ability to counterbalance pro-inflammatory cytokine expression. Clinical and animal studies suggest a role for IL-10 in modifying depressive behavior. Murine restraint stress (RST) is regularly employed in the study of behavioral and biological symptoms associated with depressive disorders. While responses to acute RST exposure have been widely characterized, few studies have examined the ongoing and longitudinal effects of extended RST and fewer still have examined the lasting impact during the post-stress period. Consistent with clinical data, we report that a protocol of prolonged murine RST produced altered cytokine profiles similar to those observed in major depressive disorder. Parallel to these changes in circulating cytokines, IL-10 mRNA expression was diminished in the cortex and hippocampus throughout the stress period and following cessation of RST. Moreover, chronic RST promoted depressive-like behavior throughout the 28-day stress period and these depressive-like complications were maintained weeks after cessation of RST. Because of the correlation between IL-10 suppression and depressive behavior and because many successful antidepressant therapies yield increases in IL-10, we examined the effects of IL-10 treatment on RST-induced behavioral changes. Behavioral deficits induced by RST were reversed by exogenous administration of recombinant IL-10. This work provides one of the first reports describing the biological and behavioral impact following prolonged RST and, taken together, this study provides details on the correlation between responses to chronic RST and those seen in depressive disorders.

【 授权许可】

CC BY