Interleukin-4 is a participant in the regulation of depressive-like behavior.
Inflammatory immune activation has been frequently associated with the development of major depression. Microglia might serve as an important interface in this immune system-to-brain communication. Interleukin-4, the major Th2 type cytokine, might be protective against depression due to its ability to counter-regulate inflammation and to inhibit serotonin transporter activity. By using an Interferon-α mouse model, we show that a decreased IL-4 responsiveness of microglia was specifically related to the development of depressive-like behavior. IL-4 deficient mice in a BALB/cJ background showed a considerable increase of depressive-like behavior in the forced swim (FST) and tail suspension test (TST) and reduced avoidance behavior in an active avoidance task. Prior conditioning with unescapable foot shocks further decreased avoidance behavior (learned helplessness) but to a similar level as in the wild type strain. IFN-α treatment was not able to further enhance the already increased level of depressive-like behavior in the FST and TST. Thus, IL-4 seems to be a critical participant in the regulation of depressive-like behavior in an untreated baseline condition. Increase of depressive-like behavior during inflammation in wild-type mice might be mediated to some extent by a reduction of IL-4 signaling.
Laboratory of Psychoneuroimmunology, Department of Psychiatry, Center of Clinical Research 1 (ZKF1 2/052), Universitätsstraße 150, Ruhr University Bochum, D-44801 Bochum, Germany. Electronic address: simonewachholz@aol.com.
Simone
S
Wachholz
Laboratory of Psychoneuroimmunology, Department of Psychiatry, Center of Clinical Research 1 (ZKF1 2/052), Universitätsstraße 150, Ruhr University Bochum, D-44801 Bochum, Germany. Electronic address: alexandra.gerhardt@rub.de.
Alexandra
A
Knorr
Laboratory of Psychoneuroimmunology, Department of Psychiatry, Center of Clinical Research 1 (ZKF1 2/052), Universitätsstraße 150, Ruhr University Bochum, D-44801 Bochum, Germany. Electronic address: leonie_mengert@hotmail.com.
Leonie
L
Mengert
Laboratory of Psychoneuroimmunology, Department of Psychiatry, Center of Clinical Research 1 (ZKF1 2/052), Universitätsstraße 150, Ruhr University Bochum, D-44801 Bochum, Germany. Electronic address: jpluemper@web.de.
Jennifer
J
Plümper
Laboratory of Psychoneuroimmunology, Department of Psychiatry, Center of Clinical Research 1 (ZKF1 2/052), Universitätsstraße 150, Ruhr University Bochum, D-44801 Bochum, Germany. Electronic address: rainer-sommer@gmx.de.
Rainer
R
Sommer
Laboratory of Psychoneuroimmunology, Department of Psychiatry, Center of Clinical Research 1 (ZKF1 2/052), Universitätsstraße 150, Ruhr University Bochum, D-44801 Bochum, Germany; Department of Psychiatry, LWL University Hospital, Ruhr-University Bochum, Alexandrinenstr. 1, D-44791 Bochum, Germany. Electronic address: georg.juckel@lwl.org.
Georg
G
Juckel
Laboratory of Psychoneuroimmunology, Department of Psychiatry, Center of Clinical Research 1 (ZKF1 2/052), Universitätsstraße 150, Ruhr University Bochum, D-44801 Bochum, Germany; Department of Psychiatry and Psychotherapy, Paracelsus Private Medical University, Nuremberg, Germany. Electronic address: astrid.friebe@rub.de.
Astrid
A
Friebe
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D003863:Depression / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D004195:Disease Models, Animal; D016898:Interferon-alpha / Q000494:pharmacology*; D015847:Interleukin-4 / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C
D016898:Interferon-alpha; D015847:Interleukin-4
Animal model; Depression; Interferon-alpha; Interleukin-4; Microglia