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
. 2024 Apr;66(3):e22479.
doi: 10.1002/dev.22479.

The role of epigenetic mechanisms in the long-term effects of early-life adversity and mother-infant relationship on physiology and behavior of offspring in laboratory rats and mice

Olga V Burenkova  1   2   3 , Elena L Grigorenko  1   2   4   5   6   7
Affiliations
Review

The role of epigenetic mechanisms in the long-term effects of early-life adversity and mother-infant relationship on physiology and behavior of offspring in laboratory rats and mice

Olga V Burenkova et al. Dev Psychobiol. 2024 Apr.

Abstract

Maternal care during the early postnatal period of altricial mammals is a key factor in the survival and adaptation of offspring to environmental conditions. Natural variations in maternal care and experimental manipulations with maternal-child relationships modeling early-life adversity (ELA) in laboratory rats and mice have a strong long-term influence on the physiology and behavior of offspring in rats and mice. This literature review is devoted to the latest research on the role of epigenetic mechanisms in these effects of ELA and mother-infant relationship, with a focus on the regulation of hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor. An important part of this review is dedicated to pharmacological interventions and epigenetic editing as tools for studying the causal role of epigenetic mechanisms in the development of physiological and behavioral profiles. A special section of the manuscript will discuss the translational potential of the discussed research.

Keywords: brain-derived neurotrophic factor; early-life adversity; enrichment; epigenetics; glucocorticoid receptors; histone deacetylase; histone deacetylase inhibitors; hypothalamic-pituitary-adrenal axis; maternal separation; neuronal plasticity.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Statement

The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Simplified scheme of the long-term effects of early-life adversity and mother-infant relationship on physiology and behavior of offspring. Note. GRs = glucocorticoid receptors; DNAm = DNA methylation; HDACi = HDAC inhibitors; HPA axis = hypothalamic-pituitary-adrenal axis; LG-ABN = licking/grooming and arched-back nursing. Activating pathways are indicated by solid lines, inhibitory with dashed ones.
See this image and copyright information in PMC

References

    1. Aisa B, Gil-Bea FJ, Marcos B, Tordera R, Lasheras B, Del Rio J, & Ramirez MJ (2009). Neonatal stress affects vulnerability of cholinergic neurons and cognition in the rat: involvement of the HPA axis. Psychoneuroendocrinology, 34(10), 1495–1505. doi: 10.1016/j.psyneuen.2009.05.003 - DOI - PubMed
    1. Aisa B, Tordera R, Lasheras B, Del Rio J, & Ramirez M (2008). Effects of maternal separation on hypothalamic–pituitary–adrenal responses, cognition and vulnerability to stress in adult female rats. Neuroscience, 154(4), 1218–1226. doi: 10.1016/j.neuroscience.2008.05.011 - DOI - PubMed
    1. Aisa B, Tordera R, Lasheras B, Del Rio J, & Ramirez MJ (2007). Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats. Psychoneuroendocrinology, 32(3), 256–266. doi: 10.1016/j.psyneuen.2006.12.013 - DOI - PubMed
    1. Albuquerque Filho MO, de Freitas BS, Garcia RC, Crivelaro PC, Schroder N, & de Lima MN (2017). Dual influences of early-life maternal deprivation on histone deacetylase activity and recognition memory in rats. Neuroscience, 344, 360–370. doi: 10.1016/j.neuroscience.2016.12.054 - DOI - PubMed
    1. Allen L, & Dwivedi Y (2020). MicroRNA mediators of early life stress vulnerability to depression and suicidal behavior. Molecular psychiatry, 25(2), 308–320. doi: 10.1038/s41380-019-0597-8 - DOI - PMC - PubMed

LinkOut - more resources