IL-6 Enhances the Activation of PI3K-AKT/mTOR-GSK-3 β by Upregulating GRPR in Hippocampal Neurons of Autistic Mice

In this study, we utilized a maternal immune activation model to investigate the effects of GRPR on PI3K signaling in the inflamed brain of ASD mice. We used HT22 cells with and without GRPR to examine the impact of GRP-GRPR on the PI3K-AKT pathway with IL-6 treatment. We analyzed a dataset of hippocampus samples from ASD mice to identify hub genes. Our results demonstrated increased expression of IL-6, GRPR, and PI3K-AKT signaling in the hippocampus of ASD mice. Additionally, we observed increased GRPR expression and PI3K-AKT/mTOR activation in HT22 cells after IL-6 treatment, but decreased expression in HT22 cells with GRPR knockdown. NetworkAnalyst identified GSK-3 β as the most crucial gene in the PI3K-AKT/mTOR pathway in the hippocampus of ASD. Furthermore, we found that IL-6 upregulated the expression of GSK-3β in HT22 cells by upregulating GRP-GRPR. Our findings suggest that IL-6 can enhance the activation of PI3K-AKT/mTOR-GSK-3β in hippocampal neurons of ASD mice by upregulating GRPR.Graphical Abstract
Source: Journal of NeuroImmune Pharmacology - Category: Drugs & Pharmacology Source Type: research