Effect of Immune Activation during Early Gestation or Late Gestation on Inhibitory Markers in Adult Male Rats

Tasnim Rahman,Crystal Meehan,Cynthia Shannon Weickert,Ulrich Schall,Deborah M Hodgson,Juanita Todd,Tertia Purves-Tyson,Patricia T Michie,Lauren Harms

doi:10.1038/s41598-020-58449-x

Abstract

People with schizophrenia exhibit deficits in inhibitory neurons and cognition. The timing of maternal immune activation (MIA) may present distinct schizophrenia-like phenotypes in progeny. We investigated whether early gestation [gestational day (GD) 10] or late gestation (GD19) MIA, via viral mimetic polyI:C, produces deficits in inhibitory neuron indices (GAD1, PVALB, SST, SSTR2 mRNAs) within cortical, striatal, and hippocampal subregions of male adult rat offspring. In situ hybridisation revealed that polyI:C offspring had: (1) SST mRNA reductions in the cingulate cortex and nucleus accumbens shell, regardless of MIA timing; (2) SSTR2 mRNA reductions in the cortex and striatum of GD19, but not GD10, MIA; (3) no alterations in cortical or striatal GAD1 mRNA of polyI:C offspring, but an expected reduction of PVALB mRNA in the infralimbic cortex, and; (4) no alterations in inhibitory markers in hippocampus. Maternal IL-6 response negatively correlated with adult offspring SST mRNA in cortex and striatum, but not hippocampus. These results show lasting inhibitory-related deficits in cortex and striatum in adult offspring from MIA. SST downregulation in specific cortical and striatal subregions, with additional deficits in somatostatin-related signalling through SSTR2, may contribute to some of the adult behavioural changes resulting from MIA and its timing.

Highlights

Neural activity between the cortex and striatum regulates motor, cognitive, and limbic function, and aspects of these modalities are perturbed in people with schizophrenia[1,2]
Long-term impacts of early gestation and late gestation maternal immune activation (MIA) on inhibitory indices within the cortex and striatum of adult rat polyribocytidilic acid (polyI):C offspring
We found PVALB mRNA reductions in the infralimbic cortex of polyI:C offspring, which aligns with previous studies that report reductions in PVALB-positive cells in the medial prefrontal cortex in both early gestation and late gestation adult[49,52]

Summary

Introduction

Neural activity between the cortex and striatum regulates motor, cognitive, and limbic function, and aspects of these modalities are perturbed in people with schizophrenia[1,2]. In the current study we investigated the effects of early gestation (GD10) or late gestation (GD19) polyI:C-induced MIA on gene expression of inhibitory indices (GAD1, PVALB, SST, and SSTR2) in the cortex, striatum, and hippocampus of adult male offspring.

Results

Conclusion