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应激相关行为检测调控的 mRNA 和 lncRNA 的共表达网络。

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

机构信息

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

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

出版信息

Psychopharmacology (Berl). 2020 Feb;237(2):571-582. doi: 10.1007/s00213-019-05390-1. Epub 2019 Nov 23.

DOI:10.1007/s00213-019-05390-1
PMID:31760461
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.

摘要

原理

设计用于研究情绪机制和发现神经精神疾病有效治疗方法的情绪相关行为测定,通常基于啮齿动物对某些威胁的自然厌恶。

目的

虽然已经对进行的序列给予了合理的关注,但很少有研究涉及行为测定本身是否会影响内在信号、基因表达以及随后的小鼠表现。

方法

我们检查了常用于焦虑和抑郁的行为测定(包括高架十字迷宫测试(EPM)、强迫游泳测试(FST)和悬尾测试(TST))的短期(1 天)和长期(7 天和 14 天)效果对行为的影响。我们还研究了重复行为测定对行为的影响。通过对 RNA 测序生成的 mRNA 和 lncRNA 转录组的综合分析,探讨了行为测定后海马体中表达谱的变化。

结果

我们发现,一次 FST 或 TST 可以引起焦虑相关行为,而重复 FST 或 TST 导致小鼠出现抑郁相关行为。改变的行为与 FST 和 TST 海马体中广泛的转录变化有关。KEGG 途径分析表明,FST 和 TST 海马体中的差异表达基因(DEGs)分别富集在焦虑和代谢相关途径中。此外,差异表达的 lncRNA,与 DEGs 相关,与 FST 海马体中的焦虑相关途径和 TST 海马体中的代谢相关途径有关。

结论

我们的研究确定了情绪相关行为测定调节的独特和共同的 mRNAs 和 lncRNAs,强调了它们之间的顺序和间隔的重要性。

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