Effects of maternal immune activation on gene expression patterns in the fetal brain
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.
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).
Published - Garbett2012p19018Transl_Psychiat.pdf
Supplemental Material - tp201224x1.xls
Supplemental Material - tp201224x2.xls