title: Genome-Wide Transcriptional Profiling and Structural Magnetic Resonance Imaging in the Maternal Immune Activation Model of Neurodevelopmental Disorders.
abstract: Prenatal exposure to maternal infection increases the risk of neurodevelopmental disorders, including schizophrenia and autism. The molecular processes underlying this pathological association, however, are only partially understood. Here, we combined unbiased genome-wide transcriptional profiling with follow-up epigenetic analyses and structural magnetic resonance imaging to explore convergent molecular and neuromorphological alterations in corticostriatal areas of adult offspring exposed to prenatal immune activation. Genome-wide transcriptional profiling revealed that prenatal immune activation caused a differential expression of 116 and 251 genes in the medial prefrontal cortex and nucleus accumbens, respectively. A large part of genes that were commonly affected in both brain areas were related to myelin functionality and stability. Subsequent epigenetic analyses indicated that altered DNA methylation of promoter regions might contribute to the differential expression of myelin-related genes. Quantitative relaxometry comparing T1, T2, and myelin water fraction revealed sparse increases in T1 relaxation times and consistent reductions in T2 relaxation times. Together, our multi-system approach demonstrates that prenatal viral-like immune activation causes myelin-related transcriptional and epigenetic changes in corticostriatal areas. Even though these abnormalities do not seem to be associated with overt white matter reduction, they may provide a molecular mechanism whereby prenatal infection can impair myelin functionality and stability.
authors: Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland.
authors: Juliet
authors: J
authors: Richetto
authors: Department of Basic and Clinical Neuroscience, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
authors: Robert
authors: R
authors: Chesters
authors: Biological Psychiatry Laboratory, IRCCS Fatebenefratelli San Giovanni di Dio, Brescia, Italy.|Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK.
authors: Annamaria
authors: A
authors: Cattaneo
authors: Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
authors: Marie A
authors: MA
authors: Labouesse
authors: Department of Basic and Clinical Neuroscience, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
authors: Ana Maria Carrillo
authors: AMC
authors: Gutierrez
authors: Department of Neuroimaging, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
authors: Tobias C
authors: TC
authors: Wood
authors: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors: Alessia
authors: A
authors: Luoni
authors: Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland.
authors: Urs
authors: U
authors: Meyer
authors: Department of Basic and Clinical Neuroscience, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
authors: Anthony
authors: A
authors: Vernon
authors: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors: Marco A
authors: MA
authors: Riva
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D015331:Cohort Studies; D019175:DNA Methylation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005865:Gestational Age; D007369:Interferon Inducers / Q000633:toxicity; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism; D065886:Neurodevelopmental Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism; D011070:Poly I-C / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology
chemical_list: D007369:Interferon Inducers; C499047:Mbp protein, mouse; C560488:Mobp protein, mouse; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D011070:Poly I-C
keywords: Magnetic resonance imaging (MRI); maternal immune activation; myelin; poly(I:C); schizophrenia; transcriptome