title: Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation.
abstract: In recent years schizophrenia has been recognized as a neurodevelopmental disorder likely involving a perinatal insult progressively affecting brain development. The poly I:C maternal immune activation (MIA) rodent model is considered as a neurodevelopmental model of schizophrenia. Using this model we and others demonstrated the association between neuroinflammation in the form of altered microglia and a schizophrenia-like endophenotype. Therapeutic intervention using the anti-inflammatory drug minocycline affected altered microglia activation and was successful in the adult offspring. However, less is known about the effect of preventive therapeutic strategies on microglia properties. Previously we found that deep brain stimulation of the medial prefrontal cortex applied pre-symptomatically to adolescence MIA rats prevented the manifestation of behavioral and structural deficits in adult rats. We here studied the effects of deep brain stimulation during adolescence on microglia properties in adulthood. We found that in the hippocampus and nucleus accumbens, but not in the medial prefrontal cortex, microglial density and soma size were increased in MIA rats. Pro-inflammatory cytokine mRNA was unchanged in all brain areas before and after implantation and stimulation. Stimulation of either the medial prefrontal cortex or the nucleus accumbens normalized microglia density and soma size in main projection areas including the hippocampus and in the area around the electrode implantation. We conclude that in parallel to an alleviation of the symptoms in the rat MIA model, deep brain stimulation has the potential to prevent the neuroinflammatory component in this disease.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty Carl Gustav Carus, Technische Universitaet Dresden, Germany.
authors.forename: Ravit
authors.initials: R
authors.lastname: Hadar
authors.affiliation: Cellular Neuroscience, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
authors.forename: Le
authors.initials: L
authors.lastname: Dong
authors.affiliation: Cellular Neuroscience, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
authors.forename: Lucia
authors.initials: L
authors.lastname: Del-Valle-Anton
authors.affiliation: Cellular Neuroscience, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
authors.forename: Dilansu
authors.initials: D
authors.lastname: Guneykaya
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty Carl Gustav Carus, Technische Universitaet Dresden, Germany; International Graduate Program Medical Neurosciences, Charité - Universitaetsmedizin Berlin, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Voget
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty Carl Gustav Carus, Technische Universitaet Dresden, Germany; International Graduate Program Medical Neurosciences, Charité - Universitaetsmedizin Berlin, Germany.
authors.forename: Henriette
authors.initials: H
authors.lastname: Edemann-Callesen
authors.affiliation: Cellular Neuroscience, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Schweibold
authors.affiliation: Cellular Neuroscience, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
authors.forename: Anais
authors.initials: A
authors.lastname: Djodari-Irani
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty Carl Gustav Carus, Technische Universitaet Dresden, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Goetz
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty Carl Gustav Carus, Technische Universitaet Dresden, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Ewing
authors.affiliation: Cellular Neuroscience, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Kettenmann
authors.affiliation: Cellular Neuroscience, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. Electronic address: susanne.wolf@mdc-berlin.de.
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Wolf
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty Carl Gustav Carus, Technische Universitaet Dresden, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Winter
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000187:drug effects; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017628:Microglia / Q000187:drug effects*; D008911:Minocycline / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000276:immunology / Q000628:therapy
chemical_list: D008911:Minocycline; D011070:Poly I-C
keywords: Deep brain stimulation; Depression; Maternal immune activation; Microglia; Schizophrenia