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Effects of maternal immune activation on gene expression patterns in the fetal brain

Garbett, K. A. and Hsiao, E. Y. and Kálmán, S. and Patterson, P. H. and Mirnics, K. (2012) Effects of maternal immune activation on gene expression patterns in the fetal brain. Translational Psychiatry, 2 . Art. No. e98. ISSN 2158-3188 . PMCID PMC3337077. http://resolver.caltech.edu/CaltechAUTHORS:20120803-134745067

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Abstract

We are exploring the mechanisms underlying how maternal infection increases the risk for schizophrenia and autism in the offspring. Several mouse models of maternal immune activation (MIA) were used to examine the immediate effects of MIA induced by influenza virus, poly(I:C) and interleukin IL-6 on the fetal brain transcriptome. Our results indicate that all three MIA treatments lead to strong and common gene expression changes in the embryonic brain. Most notably, there is an acute and transient upregulation of the α, β and γ crystallin gene family. Furthermore, levels of crystallin gene expression are correlated with the severity of MIA as assessed by placental weight. The overall gene expression changes suggest that the response to MIA is a neuroprotective attempt by the developing brain to counteract environmental stress, but at a cost of disrupting typical neuronal differentiation and axonal growth. We propose that this cascade of events might parallel the mechanisms by which environmental insults contribute to the risk of neurodevelopmental disorders such as schizophrenia and autism.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/tp.2012.24 DOIArticle
http://www.nature.com/tp/journal/v2/n4/full/tp201224a.htmlPublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337077/PubMed CentralArticle
Additional Information:© 2012 Macmillan Publishers Limited. Received 09 November 2011; revised 27 February 2012; accepted 03 March 2012. Published online 3 April 2012. We are thankful for the microarray work performed by the Genome Sciences Resource at Vanderbilt University and for valuable comments of the manuscript provided by Martin J Schmidt. The experiments were supported by NIH R01 MH067234 (KM), MH079299 (KM), Cure Autism Now (PHP), McKnight Foundation Neuroscience of Brain Disorder Award (PHP), NIH RO1 MH067978 (PHP), Autism Speaks Dennis Weatherstone Pre-Doctoral Fellowship (EYH) and NRSA 5 T32GM07737 (EYH).
Funders:
Funding AgencyGrant Number
NIHR01 MH067234
NIHMH079299
Cure Autism NowUNSPECIFIED
McKnight FoundationUNSPECIFIED
NIHRO1 MH067978
Autism Speaks Dennis Weatherstone Pre-Doctoral FellowshipUNSPECIFIED
NIH5 T32GM07737
Subject Keywords:autism; brain; crystallin; gene expression; maternal immune activation; schizophrenia
PubMed Central ID:PMC3337077
Record Number:CaltechAUTHORS:20120803-134745067
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20120803-134745067
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:32920
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:03 Aug 2012 22:38
Last Modified:30 Dec 2015 22:23

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