title: Longitudinal in vivo maturational changes of metabolites in the prefrontal cortex of rats exposed to polyinosinic-polycytidylic acid in utero.
abstract: Proton magnetic resonance spectroscopy ((1)H MRS) studies in schizophrenia patients generally report decreased levels of N-acetyl-aspartate (NAA), glutamate and glutathione, particularly in frontal cortex. However, these data are inconsistent in part due to confounds associated with clinical samples. The lack of validated diagnostic biomarkers also hampers analysis of the neurodevelopmental trajectory of neurochemical abnormalities. Rodent models are powerful tools to address these issues, particularly when combined with (1)H MRS (clinically comparable technology). We investigated the trajectory of metabolic changes in the prefrontal cortex during brain maturation from adolescence to adulthood in vivo using (1)H MRS in rats exposed prenatally to polyinosinic-polycytidylic acid (POL), a rodent model of maternal immune activation (MIA), an epidemiological risk factor for several psychiatric disorders with a neurodevelopmental origin. Longitudinal in vivo (1)H MRS revealed a significant decrease in PFC levels of GSH and taurine in adult, but not adolescent rats. Significant age×MIA interactions for PFC levels of NAA were also observed. These data replicate some deficits observed in the PFC of patients with schizophrenia. There were no significant changes in the levels of glutamate or any other metabolite. These data suggest prenatal exposure to POL leads to subtle metabolic perturbations of the normal maturing PFC, which may be related to subsequent behavioural abnormalities. Further work is however required to examine any potential confound of shipping stress on the presumed imbalances in PFC metabolites in POL-exposed offspring. Testing the interactions between MIA with stress or genetic risk variants will also be an important advance.
authors.affiliation: King's College London, Institute of Psychiatry Psychology and Neuroscience, Department of Psychosis Studies, De Crespigny Park, London SE5 8AF, UK. Electronic address: anthony.vernon@kcl.ac.uk.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Vernon
authors.affiliation: King's College London, Institute of Psychiatry, Department of Neuroimaging, Centre for Neuroimaging Sciences, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Po-Wah
authors.initials: PW
authors.lastname: So
authors.affiliation: King's College London, Institute of Psychiatry, Department of Neuroimaging, Centre for Neuroimaging Sciences, De Crespigny Park, London SE5 8AF, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lythgoe
authors.affiliation: King's College London, Institute of Psychiatry Psychology and Neuroscience, Department of Psychosis Studies, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Winfred
authors.initials: W
authors.lastname: Chege
authors.affiliation: King's College London, Institute of Psychiatry Psychology and Neuroscience, Department of Basic and Clinical Neuroscience, The James Black Centre, 125 Coldharbour Lane, London SE5 9NU, UK.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cooper
authors.affiliation: King's College London, Institute of Psychiatry, Department of Neuroimaging, Centre for Neuroimaging Sciences, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Steven C R
authors.initials: SC
authors.lastname: Williams
authors.affiliation: King's College London, Institute of Psychiatry Psychology and Neuroscience, Department of Psychosis Studies, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
mesh_terms: D000367:Age Factors; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D018698:Glutamic Acid; D005978:Glutathione / Q000378:metabolism*; D007369:Interferon Inducers / Q000633:toxicity*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011070:Poly I-C / Q000633:toxicity*; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects; D013654:Taurine / Q000378:metabolism
chemical_list: D007369:Interferon Inducers; D011522:Protons; D013654:Taurine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D005978:Glutathione; D011070:Poly I-C
keywords: Glutathione; Magnetic resonance spectroscopy; Maternal immune activation; Poly (I:C); Schizophrenia; Taurine