title: Altered microglia morphology and higher resilience to stress-induced depression-like behavior in CX3CR1-deficient mice.
abstract: Microglia are suggested to be involved in several neuropsychiatric diseases. Indeed changes in microglia morphology have been reported in different mouse models of depression. A crucial regulatory system for microglia function is the well-defined CX3C axis. Thus, we aimed to clarify the role of microglia and CX3CR1 in depressive behavior by subjecting CX3CR1-deficient mice to a particular chronic despair model (CDM) paradigm known to exhibit face validity to major depressive disorder. In wild-type mice we observed the development of chronic depressive-like behavior after 5days of repetitive swim stress. 3D-reconstructions of Iba-1-labeled microglia in the dentate molecular layer revealed that behavioral effects were associated with changes in microglia morphology towards a state of hyper-ramification. Chronic treatment with the anti-depressant venlafaxine ameliorated depression-like behavior and restored microglia morphology. In contrast, CX3CR1 deficient mice showed a clear resistance to either (i) stress-induced depressive-like behavior, (ii) changes in microglia morphology and (iii) antidepressant treatment. Our data point towards a role of hyper-ramified microglia in the etiology of chronic depression. The lack of effects in CX3CR1 deficient mice suggests that microglia hyper-ramification is controlled by neuron-microglia signaling via the CX3C axis. However, it remains to be elucidated how hyper-ramified microglia contribute to depressive-like behavior.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Freiburg, Freiburg, Germany. Electronic address: sabine.hellwig@uniklinik-freiburg.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hellwig
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Brioschi
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Dieni
authors.affiliation: Centre of Geriatrics and Gerontology, University Hospital Freiburg, Freiburg, Germany; Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Frings
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Masuch
authors.affiliation: Department of Neuropathology, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Blank
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Freiburg, Freiburg, Germany; Department for Neuroscience, University Medical Center Groningen, University of Groningen, Netherlands. Electronic address: knut.biber@uniklinik-freiburg.de.
authors.forename: Knut
authors.initials: K
authors.lastname: Biber
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D054428:Chemokine CX3CL1 / Q000172:deficiency*; D003865:Major Depressive Disorder / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology*; D013315:Stress, Psychological / Q000150:complications*
chemical_list: D054428:Chemokine CX3CL1
keywords: CX3CL1; CX3CR1; Depression; Fractalkine; Microglia; Stress