Maternal Immune Activation Alters Fetal Brain Development through Interleukin-6:
Schizophrenia and autism are thought to result from the interaction between a susceptibility genotype and environmental risk factors. The offspring of women who experience infection while pregnant have an increased risk for these disorders. Maternal immune activation (MIA) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism, making MIA a useful model of the disorders. However, the mechanism by which MIA causes long-term behavioral deficits in the offspring is unknown. Here we show that the cytokine interleukin-6 (IL-6) is critical for mediating the behavioral and transcriptional changes in the offspring. A single maternal injection of IL-6 on day 12.5 of mouse pregnancy causes prepulse inhibition (PPI) and latent inhibition (LI) deficits in the adult offspring. Moreover, coadministration of an anti-IL-6 antibody in the poly(I:C) model of MIA prevents the PPI, LI, and exploratory and social deficits caused by poly(I:C) and normalizes the associated changes in gene expression in the brains of adult offspring. Finally, MIA in IL-6 knock-out mice does not result in several of the behavioral changes seen in the offspring of wild-type mice after MIA. The identification of IL-6 as a key intermediary should aid in the molecular dissection of the pathways whereby MIA alters fetal brain development, which can shed new light on the pathophysiological mechanisms that predispose to schizophrenia and autism.
From ScienceDaily:
Since schizophrenia and autism have a strong (though elusive) genetic component, there is no absolute certainty that infection will cause the disorders in a given case, but it is believed that as many as 21 percent of known cases of schizophrenia may have been triggered in this way. The conclusion is that susceptibility to these disorders is increased by something that occurs to mother or fetus during a bout with the flu.
Now, researchers have isolated a protein that plays a pivotal role in that dire chain of events. A paper containing their results, "Maternal immune activation alters fetal brain development through interleukin-6," will be published in the Oct. 3 issue of the Journal of Neuroscience.
Surprisingly, the finger of blame does not point at the virus itself. Since influenza infection is generally restricted to the mother's respiratory tract, the team speculated that what acts as the mediator is not the mother's infection per se but something in her immune response to it.
Many diseases which have environmental components of variation may actually be due in part to infections....
Related: Toxoplasma gondii.
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A similar hypothesis has been raised about male homosexuality. Its based on the finding that fraternal birth order is the #1 most important factor known so far that affects the probability of being gay. The more biological older brothers one has, the more likely one is, if male, to be gay. This can be understood by assuming that certain mothers launch immune responses to male specific antigens.