Trends in Molecular Medicine
ReviewMaternal infection and immune involvement in autism
Section snippets
Maternal infection and autism
There is little public awareness that infection during pregnancy significantly increases the probability of the offspring becoming schizophrenic. In fact, it has been estimated that if viral (influenza, Herpes simplex virus, rubella), bacterial (urinary tract) and parasitic (toxoplasma) infections could be prevented in pregnant women, >30% of schizophrenia cases could be eliminated [1]. The public health implications are enormous, but not widely recognized [2]. Similarly, there is little public
Immune-related abnormalities in autism
A variety of organ systems exhibit inflammatory-like changes in autism. Evidence comes from quantifying immune-related proteins and RNAs, as well as immunohistochemistry. Findings from epidemiology are also relevant.
Animal models of the maternal infection risk factor
The maternal infection risk factor is currently being studied in mice, rats and monkeys. These experiments involve infecting the mother or simply activating her immune system in the absence of pathogens.
Gene–environment interactions
Many mental disorders have been attributed in part to genes that increase susceptibility to environmental risk factors. To date, however, there is little evidence for such gene–environment interactions. Therefore, it is of interest that mice heterozygous for the tuberous sclerosis 2 (Tsc2) gene display a social interaction deficit only when they are born to mothers treated with poly(I:C) [37]. That is, this behavioral deficit is most severe when the MIA environmental risk factor is combined
Therapeutic manipulations
The findings summarized above demonstrate that the maternal infection and MIA models display face (similar symptoms) and construct (similar cause) values for both autism and schizophrenia. These models can have a predictive value as well. For example, the manipulation of cytokines during pregnancy can prevent the development of abnormal behaviors in the offspring in the poly(I:C) and LPS models. In addition, pretreatment of pregnant rats with N-acetyl-cysteine, which increases calcium influx
Concluding remarks
A variety of techniques has been used to demonstrate the presence of a subclinical, inflammatory-like state in the brain, CSF and peripheral immune system in many ASD samples. There is also evidence of abnormalities in the GI tract, although the prevalence and precise phenotype in that system remain to be determined. Mouse and rat models that mimic the autism maternal infection risk factor display face, construct and predictive validity for ASD. Many of the symptoms in these rodent models are
Acknowledgments
The work cited from the author's laboratory was supported by the National Institute of Mental Health, the California Institute of Regenerative Medicine and the Autism Speaks and Binational Science foundations. Owing to space limitations, reviews are cited rather than primary research articles wherever possible.
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