Co-expression Network of mRNAs and lncRNAs Regulated by Stress-Linked Behavioral Assays

Abstract

Rationale: Mood-related behavioral assays, designed typically on rodents’ natural aversion to certain threats, are useful in studying the mechanisms of mood and in discovering effective treatments for neuropsychiatric disorders. Objectives: Although reasonable attention has been paid to the conducted sequence, few studies address the argument whether a behavioral assay itself affects the intrinsic signaling, gene expression, and the subsequent performance of mice. Methods: We examined the short- (1 day) and long-term effects (7 and 14 days) of commonly used behavioral assays for anxiety and depression, including the elevated plus maze test (EPM), forced swimming test (FST), and tail suspension test (TST), on behaviors. We also investigated the effects of repeated behavioral assays on behaviors. The alterations in the expression profiles in the hippocampus experienced behavioral assays were explored via the integrative analysis of mRNA and lncRNA transcriptomes generated by RNA sequencing. Results: We found that one FST or TST can induce anxiety-related behaviors, while repeated FST or TST resulted in depression-related behaviors in mice. The altered behaviors were associated with extensive transcriptional alterations in the FST and TST hippocampus of mice. KEGG pathway analyses indicated that differentially expressed genes (DEGs) in the FST and TST hippocampus were enriched in anxiety- and metabolic-related pathways, respectively. Moreover, differentially expressed lncRNAs, showing correlations with DEGs, were linked to anxiety-related pathways in the FST hippocampus and metabolic-related pathways in the TST hippocampus. Conclusions: Our study identified the unique and shared mRNAs and lncRNAs regulated by mood-related behavioral assays, emphasizing the importance of the sequence of and intervals between them.