Poly(I:C) alters placental and fetal brain amino acid transport in a rat model of maternal immune activation.

Abstract

Maternal immune activation (MIA) during pregnancy is associated with increased chances of neurodevelopmental disorders including schizophrenia and autism spectrum disorder (ASD). However, the exact mechanism through which MIA contributes to altered neurodevelopment is unknown. Due to the important role that amino acids play in neurodevelopment, alteredamino acid transport could play a role in neurodevelopmental disorders. Indeed, altered plasma concentrations of multiple amino acids have been reported in individuals with ASD or schizophrenia. Therefore,our objective was to determine whether virally mediated MIA induces changes in amino acid transporters in the placenta and fetal brain. Pregnant rats were administered poly(I:C) on gestational day 14, and placental and fetal tissues were collected 6, 24, and 48hours later. Amino acid transporter expression was measured in the placenta and fetal brain using qPCR, Western blotting, and Simple Western. Free amino acid concentrations in the fetal brain were quantified using HPLC. Poly(I:C) increased mRNA expression of several amino acid transporters in the placenta and fetal brain over these timepoints. Conversely, poly(I:C) imposed significant decreases in the protein expression of ASCT1 and EAAT2 in placenta and expression of SNAT5, EAAT1, and GLYT1 in fetal brain. Functional consequences of altered transporter expression were demonstrated through widespread changes in the concentrations of free amino acids in the fetal brains. Together, these results represent novel findings with the poly(I:C) MIA model and contribute to the understanding of how MIA during pregnancy potentially leads to neurodevelopmental disorders.