title: Using a maternal immune stimulation model of schizophrenia to study behavioral and neurobiological alterations over the developmental course.
abstract: A growing body of evidence sheds light on the neurodevelopmental nature of schizophrenia with symptoms typically emerging during late adolescence or young adulthood. We compared the pre-symptomatic adolescence period with the full symptomatic period of adulthood at the behavioral and neurobiological level in the poly I:C maternal immune stimulation (MIS) rat model of schizophrenia. We found that in MIS-rats impaired sensorimotor gating, as reflected in disrupted prepusle inhibition (PPI), emerged post-pubertally, with behavioral deficits being only recorded in adulthood but not during adolescence. Using post mortem HPLC we found that MIS-rats show distinct dopamine and serotonin changes in the medial prefrontal cortex (mPFC), nucleus accumbens (Nacc), caudate putamen, globus pallidus, and hippocampus. Further, FDG-PET has shown that these animals had lower glucose uptake in the ventral hippocampus and PFC and a higher metabolism in the amygdala and Nacc when compared to controls. Changes in neurotransmission and metabolic activity varied across brain structures with respect to first appearance and further development. In the mPFC and Hipp, MIS-rats showed abnormal neurochemical and metabolic activity prior to and with the development of behavioral deficits in both adolescent and adult states, reflecting an early impairment of these regions. In contrast, biochemical alteration in the Nacc and globus pallidus developed as a matter of age. Our findings suggest that MIS-induced neurochemical and metabolic changes are neurodevelopmental in nature and either progressive or non-progressive and that the behavioral deficits manifest as these abnormalities increase.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany.
authors.forename: Ravit
authors.initials: R
authors.lastname: Hadar
authors.affiliation: Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Soto-Montenegro
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Götz
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Wieske
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Sohr
authors.affiliation: Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Desco
authors.affiliation: Centre for Addiction and Mental Health, Division of Neurosurgery, University of Toronto, Toronto, Canada.
authors.forename: Clement
authors.initials: C
authors.lastname: Hamani
authors.affiliation: School of Psychological Sciences and Sagol School of NeuroscienceTel-Aviv UniversityTel-Aviv, Israel.
authors.forename: Ina
authors.initials: I
authors.lastname: Weiner
authors.affiliation: Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Pascau
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany. Electronic address: christine.winter@uniklinikum-dresden.de.
authors.forename: Christine
authors.initials: C
authors.lastname: Winter
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000254:growth & development* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D008297:Male; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D019275:Radiopharmaceuticals; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000502:physiology; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000503:physiopathology*; D055139:Sensory Gating / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D012701:Serotonin; D005947:Glucose; D004298:Dopamine
keywords: FDG-PET; Neurobiological trajectories; Neurotransmission; Poly I:C; Schizophrenia; Sensorimotor deficits