Effect of maternal immune activation and sex on electrophysiological features related to Schizophrenia

Abstract

Maternal immune activation (MIA) in response to gestational infection is a risk factor for the development of schizophrenia in offspring. Previous studies have shown that MIA in rats or mice, induced by the non-infectious viral mimic Poly(I:C), produces a wide-range of schizophrenia-like behavioural alterations in the offspring. The current study investigated the impact of MIA on two electrophysiological features altered in schizophrenia, gamma activity and mismatch negativity (MMN). Pregnant Wistar rats were exposed to either Poly(I:C) (MIA) or saline during late gestation (gestational day 19). Reliable ASSRs were found from 40 to 80 Hz. No significant treatment or sex effects were found for ASSRs. MMN responses were found and female animals had higher overall responses than males early in the MMN waveform, a novel finding. However, no significant treatment effects were found for any MMN component. A multiple hit model of MIA, or a two-hit model of a variety of risk factors might be employed in the future to produce more observable alterations. Our novel findings of sex differences suggest that animal research should consistently include both sexes to improve the validity of current models of schizophrenia.