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Modeling the maternal infection risk factor for schizophrenia and autism in mice

Patterson, Paul H. (2012) Modeling the maternal infection risk factor for schizophrenia and autism in mice. International Journal of Developmental Neuroscience, 30 (8). pp. 628-629. ISSN 0736-5748. http://resolver.caltech.edu/CaltechAUTHORS:20130222-100615544

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Abstract

Several types of maternal infection (influenza, rubella, genital and reproductive system viruses, bacteria) are associated with increased risk of schizophrenia or autism in the offspring. Modeling this risk factor in mice using influenza infection or activation of the dam's immune system by injection of the double stranded, synthetic RNA, poly(I:C) yields offspring with characteristic features of these disorders. These include behaviors (enhanced anxiety and stereotyped/compulsive behaviors, and deficits in social interaction, communication, prepulse inhibition, latent inhibition, learning) and neuropathology (parvalbumin and Purkinje cell deficits, enlarged ventricles). The cytokine IL-6 is a key mediator of the effects of poly(I:C)-induced maternal immune activation (MIA) on the fetus, as shown by blocking or genetically inactivating IL-6 in the MIA dam. Moreover, MIA activates downstream IL-6 signaling pathways in the placenta, leading to important changes in placental immune cells and endocrine functions. In addition, IL-6 and several other cytokines are induced in both the placenta and fetal brain. Consistent with reports of alterations in the immune system in schizophrenia and autism, we find that MIA leads to significant changes in lymphocytes from the spleen and mesenteric lymph node of adult offspring. As is the case a subset of autistic children, MIA offspring also exhibit gastrointestinal pathology. Thus, the MIA model has face and construct validity for schizophrenia and autism, and is proving useful for exploring the mechanism of how the maternal infection risk factor alters fetal brain and immune system development.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.ijdevneu.2012.10.072DOIArticle
http://www.sciencedirect.com/science/article/pii/S073657481200545XPublisherArticle
Additional Information:© 2012 Published by Elsevier Ltd. Supported by the NIMH, the California Institute for Regenerative Medicine, Autism Speaks, and the Binational Science Foundation.
Funders:
Funding AgencyGrant Number
National Institute of Mental Health (NIMH)UNSPECIFIED
California Institute for Regenerative Medicine (CIRM)UNSPECIFIED
Autism SpeaksUNSPECIFIED
Binational Science Foundation (USA-Israel)UNSPECIFIED
Record Number:CaltechAUTHORS:20130222-100615544
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20130222-100615544
Official Citation:Paul H. Patterson, Modeling the maternal infection risk factor for schizophrenia and autism in mice, International Journal of Developmental Neuroscience, Volume 30, Issue 8, December 2012, Pages 628-629, ISSN 0736-5748, 10.1016/j.ijdevneu.2012.10.072. (http://www.sciencedirect.com/science/article/pii/S073657481200545X)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:37072
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:22 Feb 2013 18:31
Last Modified:30 Dec 2015 22:35

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