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Epigenetic Mechanisms of Adverse Neurodevelopment in Response to Lead Exposure and Prenatal Stress and the Combination: The Road Ahead

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Epigenetics, the Environment, and Children’s Health Across Lifespans

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Abstract

Risk factors for adverse child neurodevelopment such as elevated lead exposure and prenatal stress are often co-occurring or sequentially occurring in the human environment. They also have overlapping biological targets that likely underlie the similarity of their adverse behavioral consequences. This overlap also provides a biological infrastructure for their potential interactions and enhanced and/or cumulative toxicity. Effects of both developmental lead exposure and prenatal stress can be lifelong and are consistent with early fetal reprogramming via epigenetic changes, and multigenerational and transgenerational consequences of each have been suggested. While an accumulating body of evidence now documents the potential for epigenetic reprogramming in response to maternal stressors both in human and animal studies, information on the potential for similar mechanisms in response to developmental lead exposure is still sparse. Defining the extent to which epigenetic reprogramming underlies the protracted neurodevelopmental consequences of these risk factors will need to take into account the potential for plasticity of effects, differences in outcome by sex and by brain region and by timing of exposure to the risk factor(s), and, importantly, the modifying influence of behavioral experiences on epigenetic profiles. Furthermore, critical to ultimately understanding the consequences of these risk factors for human populations will be an understanding of epigenetic outcomes in response to combined exposures to such risk factors. The determination of how/what behaviors modify epigenetic profiles in the brain offers the opportunity to devise therapeutic behavioral interventions to facilitate resilience.

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Authors and Affiliations

  1. Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Jay S. Schneider PhD

  2. Department of Environmental Medicine, University of Rochester School of Medicine, Box EHSC, Rochester, NY, 14642, USA

    Deborah A. Cory-Slechta PhD

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  1. Jay S. Schneider PhD
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Correspondence to Jay S. Schneider PhD .

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  1. Pfeiffer University, Morrisville, North Carolina, USA

    David Hollar

Abbreviations

Abbreviations

5hmC:

5-Hydroxymethylcytosine

5mC:

5-Methylcytosin

Aβ:

Amyloid-β

AβPP:

Amyloid-β protein precursor

AD:

Alzheimer’s disease

ALAD:

Aminolevulinic acid dehydratase

BACE1:

Beta-secretase 1

BDNF:

Brain-derived neurotrophic factor

CNS:

Central nervous system

CpG:

–C–phosphate–G–

CRF:

Corticotropin-releasing factor

DNA:

Deoxyribonucleic acid

DNMTs:

DNA methyltransferases

DOPAC:

3,4-Dihydroxyphenylacetic acid

GR:

Glucocorticoid receptor

HCY:

Homocysteine

hESCs:

Human embryonic stem cells

HPA axis:

Hypothalamic–pituitary–adrenal axis

IQ:

Intelligence quotient

NMDA:

n-methyl-d-aspartate

SES:

Socioeconomic status

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Schneider, J.S., Cory-Slechta, D.A. (2016). Epigenetic Mechanisms of Adverse Neurodevelopment in Response to Lead Exposure and Prenatal Stress and the Combination: The Road Ahead. In: Hollar, D. (eds) Epigenetics, the Environment, and Children’s Health Across Lifespans. Springer, Cham. https://doi.org/10.1007/978-3-319-25325-1_10

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