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

Juliet Richetto, Robert Chesters, Annamaria Cattaneo, Marie A Labouesse, Ana Maria Carrillo Gutierrez, Tobias C Wood, Alessia Luoni, Urs Meyer, Anthony Vernon, Marco A. Riva

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalCerebral Cortex
DOIs
Publication statusE-pub ahead of print - Oct 23 2016

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Myelin Sheath
Mothers
Magnetic Resonance Imaging
Genome
Epigenomics
Genes
Maternal Exposure
Nucleus Accumbens
DNA Methylation
Pathologic Processes
Autistic Disorder
Infection
Prefrontal Cortex
Genetic Promoter Regions
Schizophrenia
Neurodevelopmental Disorders
Water
Brain

Keywords

  • Journal Article

Cite this

Genome-Wide Transcriptional Profiling and Structural Magnetic Resonance Imaging in the Maternal Immune Activation Model of Neurodevelopmental Disorders. / Richetto, Juliet; Chesters, Robert; Cattaneo, Annamaria; Labouesse, Marie A; Gutierrez, Ana Maria Carrillo; Wood, Tobias C; Luoni, Alessia; Meyer, Urs; Vernon, Anthony; Riva, Marco A.

In: Cerebral Cortex, 23.10.2016.

Research output: Contribution to journalArticle

Richetto, Juliet ; Chesters, Robert ; Cattaneo, Annamaria ; Labouesse, Marie A ; Gutierrez, Ana Maria Carrillo ; Wood, Tobias C ; Luoni, Alessia ; Meyer, Urs ; Vernon, Anthony ; Riva, Marco A. / Genome-Wide Transcriptional Profiling and Structural Magnetic Resonance Imaging in the Maternal Immune Activation Model of Neurodevelopmental Disorders. In: Cerebral Cortex. 2016.
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