Effect of high mobility group box 1 pathway inhibition on gene expression in the prefrontal cortex of mice exposed to alcohol

Abstract

Introduction

The high mobility group box 1 (HMGB1) pathway plays a pivotal role in the development of alcohol-induced brain injury. Glycyrrhizinic acid (GlyA) is widely regarded as an inhibitor of HMGB1. The objective is to investigate the impact on gene expression in the prefrontal cortex,we sequenced the transcriptome in control, alcohol-exposed, and HMGB1-inhibited groups of mice. We verified our findings by real-time quantitative PCR (qRT-PCR).

Methods

An alcohol exposure model was established in mice by intraperitoneal injection of alcohol. Transcriptome sequencing and bioinformatics analyses were performed on prefrontal cortex tissue. Kyoto Encyclopedia of Genes and Genomes analysis was performed to identify pivotal pathways of differentially expressed genes. The role of relevant genes was verified by qRT-PCR.

Results

Expression of genes involved in the neuroactive ligand–receptor interaction pathway exhibited an increase in mice from the alcohol-exposed group. However, there were no significant differences observed in the expression of these genes between control and those receiving an intraperitoneal injection of alcohol along with a HMGB1 inhibitor. Mice in the alcohol-exposed group showed increased gene expression of Cysltr2, Chrna6, Chrna3, Chrnb4, and Pmch. Expression of these genes was decreased in mice injected with HMGB1 inhibitor.

Significance

Our study demonstrates that alcohol primarily influences gene expression in the prefrontal cortex of mice through the neuroactive ligand–receptor interaction pathway. HMGB1 inhibitor effectively inhibited the expression of this pathway. This study provides a novel route for drug development in alcohol-induced brain injury.