Investigation of MRNA expression levels of AMPA receptor genes in mice exposed to maternal stress

Early-life stress may predispose to psychopathological problems such as antisocial behaviours and personality disorders that continue throughout life. Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are activated by binding with glutamate. According to prediction algorithms, miR-124-3p encodes subunits of Gria2-4 and Gria1 (non-target) AMPA receptors among the targets of miR-124-3p with high scores. We investigated Gria1-4 gene expression in the hippocampus and blood of mice with maternal stress, inspired by our previous research showing raised miR-124-3p levels in these same mice. This study examined control, maternal separation (MS), and maternal separation with unpredictable maternal stress (MSUS). The MS and MSUS groups experienced unpredictable separation from their dams during postnatal days 1-14. The researchers analysed RNA from the hippocampus and blood samples of mice sacrificed on PND35 using qPCR and One-Way ANOVA tests in GraphPad Prism. It was found that Gria2 and Gria3 mRNA expression levels in the hippocampus decreased in the MS (p=0.0071, p=0.0001, respectively) and MSUS (p<0.0001, p<0.0001, respectively) groups in both females and males compared to the control. In contrast, Gria4 mRNA expression decreased in the MS and MSUS groups in females and increased in MSUS males (p=0.0094). However, in females, Gria1 mRNA expression level decreased in the MS (p=0.0021) and MSUS groups, while in males of the MS and MSUS groups, Gria1 and Gria4 mRNA expression levels increased compared to controls. In blood samples, Gria2 mRNA expression level did not change in females, Gria3 increased in MS and MSUS groups, and Gria2-3 MS increased in males. Gria1 mRNA expression level was increased in the MSUS group (p<0.0001), while Gria4 was decreased (p=0.0161) in both genders compared to the control. The study found that miR-124-3p increases in the hippocampus and its targets decrease, but no changes were seen in the blood. The mRNA levels of Gria4 and Gria1 in the blood were significantly different in the litter of stressed mothers, and these genes could serve as potential biomarkers for detecting maternal stress during the neonatal period.