Maternal infection and the offspring brain.

Editor's Note: These short reviews of a recent paper in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to mimic the journal clubs that exist in your own departments or institutions. For more information on the format and purpose of the Journal Club, please see Review of Meyer et al. Infections are a common complication of pregnancy that can lead to miscarriage and stillbirth. Epidemiological studies have associated infections caused by virus and bacteria (e.g., influenza, diphtheria, pneumonia, varicella-zoster) with adult brain disorders, including schizophrenia, autism, mental retardation and cerebral palsy. This association is not limited to a single etiological agent, suggesting that it may be mediated by factors that are common to all infections. The primary host response to infection is inflammation: the recruitment of immune cells that, in turn, release cytokines and other immunologi-cal molecules on site and to the blood stream. Cytokines released by the maternal immune system can cross the placenta and enter the fetal circulation. It is well known that cytokines can modulate neu-ronal proliferation, survival, differentiation , and function. Thus, cytokines released by the maternal immune system (and/or the placental or fetal immune system) in response to infection may be responsible for the interaction between maternal infection during pregnancy, altered neuronal development, and mental diseases. The recent Journal of Neuroscience paper by Meyer et al. (2006) tested the hypothesis whether the effects of infection during pregnancy depend on the stage of development of the fetus and/or the maternal inflammatory response. To this aim, a synthetic analog of double-stranded RNA (polyriboinosinic-polyribocytidylic acid, PolyI:C) was injected in mouse dams at two stages of pregnancy, on gestation day 9 (GD9; mid-gestation) and GD17 (late gestation). PolyI:C is used experimentally to model viral infections because it stimulates the antiviral activities of the innate immune system (including cytokine production and induction of fever), without the confounding effects of viral infection. PolyI:C challenge resulted in pronounced elevation of both proinflam-matory and anti-inflammatory cytokines in the maternal serum [Meyer et al., their Fig. 7 The changes in cytokine mRNA levels in the fetal tissue showed that fetal brain cells can sense maternal infection at both gestational periods , but an increase in fetal cytokine expression only was observed at GD17 [Meyer et al., their Fig. 9 neuronal differentiation and survival in vitro. However, the pattern of expression of cytokine receptors and intracellular sig-naling pathways during brain development …