Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jul 25:16:1183184.
doi: 10.3389/fnmol.2023.1183184. eCollection 2023.

Epigenetic embedding of childhood adversity: mitochondrial metabolism and neurobiology of stress-related CNS diseases

Benedetta Bigio  1 , Yotam Sagi  1   2 , Olivia Barnhill  3 , Josh Dobbin  3 , Omar El Shahawy  4 , Paolo de Angelis  3 , Carla Nasca  1   2   3   5
Affiliations
Review

Epigenetic embedding of childhood adversity: mitochondrial metabolism and neurobiology of stress-related CNS diseases

Benedetta Bigio et al. Front Mol Neurosci. .

Abstract

This invited article ad memoriam of Bruce McEwen discusses emerging epigenetic mechanisms underlying the long and winding road from adverse childhood experiences to adult physiology and brain functions. The conceptual framework that we pursue suggest multidimensional biological pathways for the rapid regulation of neuroplasticity that utilize rapid non-genomic mechanisms of epigenetic programming of gene expression and modulation of metabolic function via mitochondrial metabolism. The current article also highlights how applying computational tools can foster the translation of basic neuroscience discoveries for the development of novel treatment models for mental illnesses, such as depression to slow the clinical manifestation of Alzheimer's disease. Citing an expression that many of us heard from Bruce, while "It is not possible to roll back the clock," deeper understanding of the biological pathways and mechanisms through which stress produces a lifelong vulnerability to altered mitochondrial metabolism can provide a path for compensatory neuroplasticity. The newest findings emerging from this mechanistic framework are among the latest topics we had the good fortune to discuss with Bruce the day before his sudden illness when walking to a restaurant in a surprisingly warm evening that preluded the snowstorm on December 18th, 2019. With this article, we wish to celebrate Bruce's untouched love for Neuroscience.

Keywords: acetyl-L-carnitine; cognition; depression; glutamate; hippocampus; histone; mood disorders; opioid use disorders.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Social environment and health: in pursuit of windows of epigenetic plasticity. Created with BioRender.com.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Arnold S. E., Arvanitakis Z., Macauley-Rambach S. L., Koenig A. M., Wang H. Y., Ahima R. S., et al. . (2018). Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nat. Rev. Neurol. 14, 168–181. doi: 10.1038/nrneurol.2017.185 - DOI - PMC - PubMed
    1. Bagot R. C., Parise E. M., Peña C. J., Zhang H. X., Maze I., Chaudhury D., et al. . (2015). Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression. Nat. Commun. 6:7062. doi: 10.1038/ncomms8062 - DOI - PMC - PubMed
    1. Barch D. M., Tillman R., Kelly D., Whalen D., Gilbert K., Luby J. L. (2019). Hippocampal volume and depression among young children. Psychiatry Res. Neuroimaging 288, 21–28. doi: 10.1016/j.pscychresns.2019.04.012, PMID: - DOI - PMC - PubMed
    1. Barnes C. A., Markowska A. L., Ingram D. K., Kametani H., Spangler E. L., Lemken V. J., et al. . (1990). Acetyl-1-carnitine. 2: effects on learning and memory performance of aged rats in simple and complex mazes. Neurobiol. Aging 11, 499–506. doi: 10.1016/0197-4580(90)90110-l, PMID: - DOI - PubMed
    1. Biessels G. J., Reagan L. P. (2015). Hippocampal insulin resistance and cognitive dysfunction. Nat. Rev. Neurosci. 16, 660–671. doi: 10.1038/nrn4019 - DOI - PubMed

LinkOut - more resources