title: Microglia activation is associated with IFN-α induced depressive-like behavior.
abstract: Inflammatory immune activation has been frequently associated with the development of major depression. This association was confirmed in patients receiving long-term treatment with pro-inflammatory interferon-α (IFN-α). Microglia, the resident immune cells in the brain, might serve as an important interface in this immune system-to-brain communication. The aim of the present study was to investigate the role of microglia in an IFN-α mouse model of immune-mediated depression. Male BALB/c mice were treated with daily injections of IFN-α for two weeks. Depressive-like behavior was analyzed in the forced swim and tail suspension test. Activation of microglia was measured by flow cytometry. Pro-inflammatory M1 type (MHC-II, CD40, CD54, CD80, CD86, CCR7), anti-inflammatory M2 type (CD206, CD200R), and maturation markers (CD11c, CCR7) were tested, as well as the chemokine receptor CCR2. IFN-α led to a significant increase in depressive-like behavior and expression of the pro-inflammatory surface markers MHC-II, CD86, and CD54, indicating M1 polarization. Because IFN-α-treated mice showed great individual variance in the behavioral response to IFN-α, they were further divided into vulnerable and non-vulnerable subgroups. Only IFN-α vulnerable mice (characterized by their development of depressive-like behavior in response to IFN-α) showed an increased expression of MHC-II and CD86, while CD54 was similarly enhanced in both subgroups. Thus, IFN-α-induced activation of microglia was specifically associated with depressive-like behavior.
authors.affiliation: Laboratory of Psychoneuroimmunology, Department of Psychiatry, LWL-University Hospital, Ruhr University Bochum, Bochum, Germany. Electronic address: simonewachholz@aol.com.
authors.forename: Simone
authors.initials: S
authors.lastname: Wachholz
authors.affiliation: Laboratory of Psychoneuroimmunology, Department of Psychiatry, LWL-University Hospital, Ruhr University Bochum, Bochum, Germany. Electronic address: manuela.esslinger@rub.de.
authors.forename: Manuela
authors.initials: M
authors.lastname: Eßlinger
authors.affiliation: Laboratory of Psychoneuroimmunology, Department of Psychiatry, LWL-University Hospital, Ruhr University Bochum, Bochum, Germany. Electronic address: jennifer.pluemper@rub.de.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Plümper
authors.affiliation: Laboratory of Psychoneuroimmunology, Department of Psychiatry, LWL-University Hospital, Ruhr University Bochum, Bochum, Germany. Electronic address: marie-pierre.manitz@rub.de.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Manitz
authors.affiliation: Laboratory of Psychoneuroimmunology, Department of Psychiatry, LWL-University Hospital, Ruhr University Bochum, Bochum, Germany. Electronic address: georg.juckel@wkp-lwl.org.
authors.forename: Georg
authors.initials: G
authors.lastname: Juckel
authors.affiliation: Laboratory of Psychoneuroimmunology, Department of Psychiatry, LWL-University Hospital, Ruhr University Bochum, Bochum, Germany. Electronic address: astrid.friebe@rub.de.
authors.forename: Astrid
authors.initials: A
authors.lastname: Friebe
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003863:Depression / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D016898:Interferon-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000276:immunology*
chemical_list: D007155:Immunologic Factors; D016898:Interferon-alpha
keywords: CD54; CD86; Depression; Depressive-like behavior; Interferon-alpha; MHC-II; Microglia