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Stress, microRNAs, and stress-related psychiatric disorders: an overview

Molecular Psychiatry volume 28, pages 4977–4994 (2023)Cite this article

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Abstract

Stress is a major risk factor for psychiatric disorders. During and after exposure to stressors, the stress response may have pro- or maladaptive consequences, depending on several factors related to the individual response and nature of the stressor. However, the mechanisms mediating the long-term effects of exposure to stress, which may ultimately lead to the development of stress-related disorders, are still largely unknown. Epigenetic mechanisms have been shown to mediate the effects of the environment on brain gene expression and behavior. MicroRNAs, small non-coding RNAs estimated to control the expression of about 60% of all genes by post-transcriptional regulation, are a fundamental epigenetic mechanism. Many microRNAs are expressed in the brain, where they work as fine-tuners of gene expression, with a key role in the regulation of homeostatic balance, and a likely influence on pro- or maladaptive brain changes. Here we have selected a number of microRNAs, which have been strongly implicated as mediators of the effects of stress in the brain and in the development of stress-related psychiatric disorders. For all of them recent evidence is reported, obtained from rodent stress models, manipulation of microRNAs levels with related behavioral changes, and clinical studies of stress-related psychiatric disorders. Moreover, we have performed a bioinformatic analysis of the predicted brain-expressed target genes of the microRNAs discussed, and found a central role for mechanisms involved in the regulation of synaptic function. The complex regulatory role of microRNAs has suggested their use as biomarkers for diagnosis and treatment response, as well as possible therapeutic drugs. While, microRNA-based diagnostics have registered advancements, particularly in oncology and other fields, and many biotech companies have launched miRNA therapeutics in their development pipeline, the development of microRNA-based tests and drugs for brain disorders is comparatively slower.

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Fig. 1: Stress and microRNAs in the etiology of stress-related disorders.
Fig. 2: Network analysis of the first 20 biological processes containing target genes of the nine stress-related microRNAs.
Fig. 3: The potential of microRNAs for diagnosis and therapy of stress-related psychiatric disorders.

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Acknowledgements

We thank Dr. Paolo Martini for bioinformatic analysis.

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Authors and Affiliations

  1. School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

    Laura Musazzi & Jessica Mingardi

  2. Department of Theoretical and Applied Sciences, eCampus University, Novedrate, Italy

    Alessandro Ieraci

  3. Molecular Pharmacology, Cellular and Behavioral Physiology; Dipartimento di Scienze Farmaceutiche, Università Degli Studi di Milano, Milano, Italy

    Alessandro Ieraci

  4. Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy

    Alessandro Barbon

  5. Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmaceutiche, Università Degli Studi di Milano, Milano, Italy

    Maurizio Popoli

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Musazzi, L., Mingardi, J., Ieraci, A. et al. Stress, microRNAs, and stress-related psychiatric disorders: an overview. Mol Psychiatry 28, 4977–4994 (2023). https://doi.org/10.1038/s41380-023-02139-3

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