Maternal immune activation during pregnancy increases limbic GABAA receptor immunoreactivity in the adult offspring:: Implications for schizophrenia

Prenatal exposures to a variety of infections have been associated with an increased incidence of schizophrenia. We have reported that a single injection of the synthetic cytokine releaser Polyl:C to pregnant mice produced offspring that exhibited multiple schizophrenia-related behavioral deficits in adulthood. Here, we characterized the effect of maternal inflammation during fetal brain development on adult limbic morphology and expression of GABA(A)-receptors. The Polyl:C treatment did not induce morphological abnormalities but resulted in a significant increase in GABA(A) receptor subunit alpha 2 immunoreactivity (IR) in the ventral dentate gyrus and basolateral amygdala in adult treated compared to control subjects. Correlative analyses between the a2 subunit IR in the ventral dentate gyrus and the performance in the prepulse inhibition paradigm revealed a significant correlation in controls that was however absent in the pathological condition. These results suggest that prenatal immune activation-induced disturbances of early brain development result in profound alterations in the limbic expression of GABAA receptors that may underlie the schizophrenia-related behavioral deficits in the adult mice. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.