title: Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia.
abstract: The notion that schizophrenia is a neurodevelopmental disorder in which neuropathologies evolve gradually over the developmental course indicates a potential therapeutic window during which pathophysiological processes may be modified to halt disease progression or reduce its severity. Here we used a neurodevelopmental maternal immune stimulation (MIS) rat model of schizophrenia to test whether early targeted modulatory intervention would affect schizophrenia's neurodevelopmental course. We applied deep brain stimulation (DBS) or sham stimulation to the medial prefrontal cortex (mPFC) of adolescent MIS rats and respective controls, and investigated its behavioral, biochemical, brain-structural and -metabolic effects in adulthood. We found that mPFC-DBS successfully prevented the emergence of deficits in sensorimotor gating, attentional selectivity and executive function in adulthood, as well as the enlargement of lateral ventricle volumes and mal-development of dopaminergic and serotonergic transmission. These data suggest that the mPFC may be a valuable target for effective preventive treatments. This may have significant translational value, suggesting that targeting the mPFC before the onset of psychosis via less invasive neuromodulation approaches may be a viable preventive strategy.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.|Department of Psychiatry and Psychotherapy, Division of Experimental and Molecular Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Hadar
authors.affiliation: School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Bikovski
authors.affiliation: Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.|CIBERSAM, Madrid, Spain.
authors.forename: M L
authors.initials: ML
authors.lastname: Soto-Montenegro
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schimke
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Maier
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ewing
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.|International Graduate Program Medical Neurosciences, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Voget
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Wieske
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Götz
authors.affiliation: Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.|CIBERSAM, Madrid, Spain.|Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Desco
authors.affiliation: Behavioural Neurobiology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Division of Neurosurgery, Toronto Western Hospital, Toronto, ON, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Hamani
authors.affiliation: Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.|CIBERSAM, Madrid, Spain.|Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pascau
authors.affiliation: School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Weiner
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.|Department of Psychiatry and Psychotherapy, Division of Experimental and Molecular Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Winter
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D046690:Deep Brain Stimulation / Q000379:methods / Q000523:psychology; D004195:Disease Models, Animal; D004298:Dopamine / Q000494:pharmacology; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism* / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000473:pathology; D011618:Psychotic Disorders / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D055139:Sensory Gating / Q000502:physiology
chemical_list: D018377:Neurotransmitter Agents; D004298:Dopamine