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microRNA and mRNA profiles in the amygdala are associated with stress-induced depression and resilience in juvenile mice

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Abstract

Objectives

Major depressive disorder characterized as recurrent negative mood is one of the prevalent psychiatric diseases. Chronic stress plus lack of reward may induce long-term imbalance between reward and penalty circuits in the brain, leading to persistent negative mood. Numerous individuals demonstrate resilience to chronic mild stress. Molecular mechanisms for major depression and resilience in the brain remain unclear.

Methods

After juvenile mice were treated by the chronic unpredictable mild stress (CUMS) for 4 weeks, they were screened by sucrose preference, Y-maze and forced swimming tests to examine whether their behaviors were depression-like or not. mRNA and miRNA profiles were quantified by high-throughput sequencing in amygdala tissues harvested from control, CUMS-susceptible, and CUMS-resilience mice.

Results

1.5-fold ratio in reads per kilo-base per million reads was set to be the threshold to judge the involvement of mRNAs and miRNAs in the CUMS, major depression, or resilience. In the amygdala from CUMS-susceptible mice, the expression of genes relevant to GABAergic, cholinergic, glutamatergic, dopaminergic, and serotonergic synapses was changed, as well as the expression of genes that encoded signal pathways of PI3K-Akt, calcium, cAMP, MAPK, and drug addiction was imbalanced. The expression of these genes in the amygdala form CUMS-resilience mice was less changed.

Conclusions

The downregulation of genes relevant to synaptic functions and the imbalance of intra-signaling pathway in the amygdala are associated with major depression. Consistent results through sequencing mRNA and miRNA and using different methods validate our finding and conclusion.

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Acknowledgments

Authors thank Kim Davis for proof reading during the revision. This study is funded by the National Key R&D Program of China (2016YFC1307101) and Natural Science Foundation China (81671071 and 81471123) to JHW.

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  1. Mengmeng Shen and Zhenhua Song contribute to this work equally.

Authors and Affiliations

  1. School of Pharmacy, Qingdao University, 38 Dengzhou, Qingdao, 266021, Shandong, China

    Mengmeng Shen, Zhenhua Song & Jin-Hui Wang

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

    Jin-Hui Wang

  3. Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing, 100101, China

    Jin-Hui Wang

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  1. Mengmeng Shen
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M Shen and Z Song contributed to experiments and data analyses. Jin-Hui Wang contributed to concept, project design, and paper writing.

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Correspondence to Zhenhua Song or Jin-Hui Wang.

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Shen, M., Song, Z. & Wang, JH. microRNA and mRNA profiles in the amygdala are associated with stress-induced depression and resilience in juvenile mice. Psychopharmacology 236, 2119–2142 (2019). https://doi.org/10.1007/s00213-019-05209-z

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