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Cereb Cortex. 2016 Oct 23. [Epub ahead of print]

Genome-Wide Transcriptional Profiling and Structural Magnetic Resonance Imaging in the Maternal Immune Activation Model of Neurodevelopmental Disorders.

Author information

  • 1Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland.
  • 2Department of Basic and Clinical Neuroscience, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
  • 3Biological Psychiatry Laboratory, IRCCS Fatebenefratelli San Giovanni di Dio, Brescia, Italy.
  • 4Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK.
  • 5Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
  • 6Department of Neuroimaging, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
  • 7Department of Pharmacological and Biomolecular Sciences, Universit√† degli Studi di Milano, Milan, Italy.

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.

KEYWORDS:

Magnetic resonance imaging (MRI); maternal immune activation; myelin; poly(I:C); schizophrenia; transcriptome

PMID:
27797829
DOI:
10.1093/cercor/bhw320
[PubMed - as supplied by publisher]
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