IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors.
Cytokine-dependent mechanisms in the CNS have been implicated in the pathogenesis of depression. Interleukin-6 is upregulated in depressed patients and dowregulated by antidepressants. It is, however, unknown whether IL-6 is involved in the pathogenesis of depression. We subjected IL-6-deficient mice (IL-6(-/-)) to depression-related tests (learned helplessness, forced swimming, tail suspension, sucrose preference). We also investigated IL-6 in the hippocampus of stressed wild-type mice. IL-6(-/-) mice showed reduced despair in the forced swim, and tail suspension test, and enhanced hedonic behavior. Moreover, IL-6(-/-) mice exhibited resistance to helplessness. This resistance may be caused by the lack of IL-6, because stress increased IL-6 expression in wild-type hippocampi. This suggests that IL-6 is a component in molecular mechanisms in the pathogenesis of depression. IL-6(-/-) mice represent tools to study IL-6-dependent signaling pathways in the pathophysiology of depression in vivo. Moreover, these mice may support the screening of compounds for depression by altering cytokine-mediated signaling.
Chourbaji
Sabine
S
Central Institute of Mental Health (ZI), J5, Mannheim D-68159, Germany. chourbaj@as200.zi-mannheim.de
Urani
Alexandre
A
Inta
Ioana
I
Sanchis-Segura
Carles
C
Brandwein
Christiane
C
Zink
Mathias
M
Schwaninger
Markus
M
Gass
Peter
P
D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D001923:Brain Chemistry / Q000235:genetics / Q000276:immunology; D003866:Depressive Disorder / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006380:Helplessness, Learned; D006624:Hippocampus / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013315:Stress, Psychological / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology
D015850:Interleukin-6