关键词: 产前应激, 抑郁样行为, 海马体, 转录组学

Abstract: Objective To identify differentially expressed genes (DEGs) and their expression patterns and regulatory mechanisms in the hippocampus of male rat offsprings with depression-like behavior induced by prenatal stress (PS). Methods SD rats were selected to establish a chronic restrained stress model from March to October 2022. Sucrose preference test was implemented for measurement of susceptibility to prenatal stress in offsprings (PS-S).Open field test, forced swimming test, tail hanging test were used to verify the validity of animal model and the efficacy of the screening method, respectively. High-throughput sequencing-based transcriptomic approaches were applied as powerful tools to identify and characterize gene regulatory networks in hippocampus of PS-S offspring rats in this study. After data processing and quality control, bioinformatics analysis was performed to screen and classify DEGs. Results Totally 486 DEGs were identified between PS-S group and control group, of which 230 were up-regulated genes enriched in 20 GO terms, while 256 were down-regulated genes enriched in 17 GO terms. Go terms, such as "gas transport", "hemoglobin complex", "oxygen transport", "oxygen carrier activity", were ranked highest in DEGs. Seven GO terms including "glutamate 5-kinase activity","response to oxygen-containing compound" and "retinol metabolic process" were significantly enriched both in up- and down-regulated genes. KEGG pathway analysis showed that DEGs were mainly enriched in signal pathway such as "tryptophan metabolism", "phagosome", "protein digestion and absorption", "neuroactive ligand-receptor interaction" and "fructose and mannose metabolism". These findings suggested that significant differences in gene expression of TTR, CRABP2, FABP5, AANAT and TPH1 might played a critical role in PS induced depressive-like behavior in offspring rats. Conclusion DEGs involved in retinol metabolic process, retinoid and tryptophan metabolism pathways may contribute to the pathogenesis of prenatal stress-induced depression-related behavioral alterations in rat models.

Key words: prenatal stress, depressive-like behavior, hippocampus, transcriptome