title: Evolution of structural abnormalities in the rat brain following in utero exposure to maternal immune activation: A longitudinal in vivo MRI study.
abstract: Genetic and environmental risk factors for psychiatric disorders are suggested to disrupt the trajectory of brain maturation during adolescence, leading to the development of psychopathology in adulthood. Rodent models are powerful tools to dissect the specific effects of such risk factors on brain maturational profiles, particularly when combined with Magnetic Resonance Imaging (MRI; clinically comparable technology). We therefore investigated the effect of maternal immune activation (MIA), an epidemiological risk factor for adult-onset psychiatric disorders, on rat brain maturation using atlas and tensor-based morphometry analysis of longitudinal in vivo MR images. Exposure to MIA resulted in decreases in the volume of several cortical regions, the hippocampus, amygdala, striatum, nucleus accumbens and unexpectedly, the lateral ventricles, relative to controls. In contrast, the volumes of the thalamus, ventral mesencephalon, brain stem and major white matter tracts were larger, relative to controls. These volumetric changes were maximal between post-natal day 50 and 100 with no differences between the groups thereafter. These data are consistent with and extend prior studies of brain structure in MIA-exposed rodents. Apart from the ventricular findings, these data have robust face validity to clinical imaging findings reported in studies of individuals at high clinical risk for a psychiatric disorder. Further work is now required to address the relationship of these MRI changes to behavioral dysfunction and to establish thier cellular correlates.
authors.affiliation: Department of Neuroimaging Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London SE5 8AF, UK.
authors.forename: William R
authors.initials: WR
authors.lastname: Crum
authors.affiliation: Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sawiak
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Winfred
authors.initials: W
authors.lastname: Chege
authors.affiliation: Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, 5 Cutcombe Road, London SE5 9RT, UK.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cooper
authors.affiliation: Department of Neuroimaging Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London SE5 8AF, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK.
authors.forename: Steven C R
authors.initials: SCR
authors.lastname: Williams
authors.affiliation: Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, 5 Cutcombe Road, London SE5 9RT, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK. Electronic address: anthony.vernon@kcl.ac.uk.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Vernon
mesh_terms: D000679:Amygdala / Q000473:pathology; D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D001523:Mental Disorders / Q000473:pathology; D011070:Poly I-C / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011070:Poly I-C
keywords: Cortex; Magnetic resonance imaging; Maternal immune activation; Poly(I:C); Volume; schizophrenia