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

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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.

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Funding

This work was supported by the National Natural Science Foundation of China (grant numbers 31571301, 31601027, 31872237, and 81000559).

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Author notes

  1. Jianghong Zhang, Meiying Xue and Yue Mei contributed equally to this work.

Authors and Affiliations

  1. Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China

    Jianghong Zhang, Meiying Xue, Yue Mei, Zeng Ceng, Yuanyuan Li, Huajing Teng, Zhong Sheng Sun & Yan Wang

  2. University of Chinese Academy of Science, Beijing, 100049, China

    Jianghong Zhang, Meiying Xue, Yue Mei, Zeng Ceng, Yuanyuan Li, Zhong Sheng Sun & Yan Wang

  3. Laboratory of Environmental Criteria and Risk Assessment & Environmental Standards Institute, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China

    Zhigang Li

  4. Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, 325000, China

    Yi Zhang, Na Li & Zhong Sheng Sun

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  1. Jianghong Zhang
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  2. Meiying Xue
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Contributions

YW and ZS supervised the study and analyses. YW, ZS, and JZ wrote the manuscript. JZ, YM, ZL, ZC, and YL performed the behavioral assays and statistical analysis of the data. MX, YZ, NL, and HT performed the bioinformatics analyses of RNA-Seq data.

Corresponding authors

Correspondence to Huajing Teng, Zhong Sheng Sun or Yan Wang.

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Zhang, J., Xue, M., Mei, Y. et al. Co-expression Network of mRNAs and lncRNAs Regulated by Stress-Linked Behavioral Assays. Psychopharmacology 237, 571–582 (2020). https://doi.org/10.1007/s00213-019-05390-1

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  • DOI: https://doi.org/10.1007/s00213-019-05390-1

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