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Post-stroke depression: epigenetic and epitranscriptomic modifications and their interplay with gut microbiota

Molecular Psychiatry volume 28, pages 4044–4055 (2023)Cite this article

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Abstract

Epigenetic and epitranscriptomic modifications that regulate physiological processes of an organism at the DNA and RNA levels, respectively, are novel therapeutic candidates for various neurological diseases. Gut microbiota and its metabolites are known to modulate DNA methylation and histone modifications (epigenetics), as well as RNA methylation especially N6-methyladenosine (epitranscriptomics). As gut microbiota as well as these modifications are highly dynamic across the lifespan of an organism, they are implicated in the pathogenesis of stroke and depression. The lack of specific therapeutic interventions for managing post-stroke depression emphasizes the need to identify novel molecular targets. This review highlights the interaction between the gut microbiota and epigenetic/epitranscriptomic pathways and their interplay in modulating candidate genes that are involved in post-stroke depression. This review further focuses on the three candidates, including brain-derived neurotrophic factor, ten-eleven translocation family proteins, and fat mass and obesity-associated protein based on their prevalence and pathoetiologic role in post-stroke depression.

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Fig. 1: PSD prevalence and subsequent risk factors.
Fig. 2: Epigenetic/Epitranscriptomic modifications following stroke.
Fig. 3: Clinical and preclinical data of gut microbiota alteration in stroke and depression research.
Fig. 4: Putative interplay of gut microbiota and epigenetics/epitranscriptomics in the etiology of post-stroke depression.

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Acknowledgements

This study was partially supported by NIH grants (RO1 NS101960, RO1 NS109459, and R01 NS130763), US Dept. of Veterans Affairs (VA) grant I01BX005127, American Heart Association grant 898871, and the Department of Neurological Surgery, UW-Madison. Dr. Vemuganti is the recipient of a Research Career Scientist award (IK6BX005690) from the US Department of Veterans Affairs. The authors would like to thank Dr. Suresh L Mehta and Dr. Kahlilia C Morris-Blanco for constructive criticism.

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Authors and Affiliations

  1. Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA

    Soomin Jeong, Anil K. Chokkalla, Charles K. Davis & Raghu Vemuganti

  2. Neuroscience Training Program, University of Wisconsin, Madison, WI, USA

    Soomin Jeong & Raghu Vemuganti

  3. William S. Middleton Veterans Hospital, Madison, WI, USA

    Raghu Vemuganti

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  1. Soomin Jeong
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RV and SJ contributed to the study conception and design. The initial draft of the manuscript was written by SJ. AKC, CKD and RV helped in the revisions. All authors read and approved the final manuscript.

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Correspondence to Raghu Vemuganti.

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Jeong, S., Chokkalla, A.K., Davis, C.K. et al. Post-stroke depression: epigenetic and epitranscriptomic modifications and their interplay with gut microbiota. Mol Psychiatry 28, 4044–4055 (2023). https://doi.org/10.1038/s41380-023-02099-8

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