Epigenetic and Neurological Impairments Associated with Early Life Exposure to Persistent Organic Pollutants

Abstract

The incidence of neurodevelopmental and neurodegenerative diseases worldwide has dramatically increased over the last decades. Although the aetiology remains uncertain, evidence is now growing that exposure to persistent organic pollutants during sensitive neurodevelopmental periods such as early life may be a strong risk factor, predisposing the individual to disease development later in life. Epidemiological studies have associated environmentally persistent organic pollutant exposure to brain disorders including neuropathies, cognitive, motor, and sensory impairments; neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD); and neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). In many ways, this expands the classical “Developmental Origins of Health and Disease” paradigm to include exposure to pollutants. This model has been refined over the years to give the current “three-hit” model that considers the individual's genetic factors as a first “hit.” It has an immediate interaction with the early-life exposome (including persistent organic pollutants) that can be considered to be a second “hit.” Together, these first two “hits” produce a quiescent or latent phenotype, most probably encoded in the epigenome, which has become susceptible to a third environmental “hit” in later life. It is only after the third “hit” that the increased risk of disease symptoms is crystallised. However, if the individual is exposed to a different environment in later life, they would be expected to remain healthy. In this review, we examine the effect of exposure to persistent organic pollutants and particulate matters in early life and the relationship to subsequent neurodevelopmental and neurodegenerative disorders. The roles of those environmental factors which may affect epigenetic DNA methylation and therefore influence normal neurodevelopment are then evaluated.

The COVID-19 Pandemic: Does Our Early Life Environment, Life Trajectory and Socioeconomic Status Determine Disease Susceptibility and Severity?

“…Currently, this is thought of as a "three hit model". The three "hits" are generally accepted as: (1) genetic predisposition, (2) early life environment and, (3) later life environment [14,15]. As high-quality mechanistic studies have addressed the link between the early-life period and adult disease, it is becoming clear that the immune system, particularly through chronic low-grade inflammation and accelerated immuno-senescence is, mechanistically, in the heat of the action.…”

Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups

“…27 DNA methylation is the most stable and well-studied epigenetic change and consists of the addition or removal of a methyl group on the CpG region (cytosine followed by guanine) which alters DNA interactions with transcriptions factors. 30,31 Particularly, subtle methylation changes during the early-life period have been associated to increased risk of developing neurodegenerative and neuropsychiatric disorders. 29 Currently, there are two major paradigms on the effect of methylation alteration in pathologies: (i) methylation changes leading to clear gene activation or silencing which is highly found in oncogenes and (ii) subtle and complex accumulation of methylation changes that are associated to disease phenotype particularly in programming non-malignant pathologies such as depression or schizophrenia.…”

“…29 Currently, there are two major paradigms on the effect of methylation alteration in pathologies: (i) methylation changes leading to clear gene activation or silencing which is highly found in oncogenes and (ii) subtle and complex accumulation of methylation changes that are associated to disease phenotype particularly in programming non-malignant pathologies such as depression or schizophrenia. 30,31 Particularly, subtle methylation changes during the early-life period have been associated to increased risk of developing neurodegenerative and neuropsychiatric disorders. 30 In humans, preterm birth has been associated to shortand long-term alterations of the epigenome landscape.…”

Introductory Chapter: Epigenetics in Summary

“…Therefore, genome activity is epigenetically modulated under exogenous influence, and the environment-dependent changes in gene activity stably propagate from one generation of cells to the next one. Epigenetic changes impact genome functions, thus affecting health and disease status and also behavior; aging-related diseases, cancer, immunity and related disorders, obesity, metabolic disorders, infertility, and cardiovascular and neurological diseases represent only few examples of environmentally dependent diseases, and the literature in the field is growing up day by day [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”