title: Schizophrenia associated sensory gating deficits develop after adolescent microglia activation.
abstract: Maternal infection during pregnancy is a well-established risk factor for schizophrenia in the adult offspring. Consistently, prenatal Poly(I:C) treatment in mice has been validated to model behavioral and neurodevelopmental abnormalities associated with schizophrenia. By using the Poly(I:C) BALB/c mouse model, we investigated the functional profile of microglia by flow cytometry in relation to progressive behavioral changes from adolescence to adulthood. Prenatal Poly(I:C) treatment induced the expected sensory gating deficits (pre-pulse inhibition (PPI) of the acoustic startle response) in 100day-old adult offspring, but only in female not in male descendants. No PPI-deficits were present in 30day-old adolescent mice. Sensory gating deficits in adult females were preceded by a strong M1-type microglia polarization pattern during puberty as determined by flow cytometric analysis of multiple pro- and anti-inflammatory surface markers. Microglia activation in females did not persist until adulthood and was absent in behaviorally unaffected male descendants. Further, the specific activation pattern of microglia was not mirrored by a similar activation of peripheral immune cells. We conclude that prenatal Poly(I:C) treatment induces post pubertal deficits in sensory gating which are specifically preceded by a pro-inflammatory activation pattern of microglia during puberty.
authors.affiliation: 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: manuela.esslinger@rub.de.
authors.forename: Manuela
authors.initials: M
authors.lastname: Eßlinger
authors.affiliation: 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: simone.wachholz@rub.de.
authors.forename: Simone
authors.initials: S
authors.lastname: Wachholz
authors.affiliation: 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: marie-pierre.manitz@rub.de.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Manitz
authors.affiliation: 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: jpluemper@web.de.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Plümper
authors.affiliation: 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.
authors.forename: Rainer
authors.initials: R
authors.lastname: Sommer
authors.affiliation: 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.
authors.forename: Georg
authors.initials: G
authors.lastname: Juckel
authors.affiliation: 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: astrid.friebe@rub.de.
authors.forename: Astrid
authors.initials: A
authors.lastname: Friebe
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000276:immunology*; D011066:Poly C / Q000008:administration & dosage; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D012559:Schizophrenia / Q000276:immunology*; D012565:Schizophrenic Psychology; D055139:Sensory Gating
chemical_list: D016207:Cytokines; D011066:Poly C
keywords: Animal model; M1; M2; Microglia; PPI; Poly(I:C); Schizophrenia