Long-term effects of wildfire smoke exposure during early life on the nasal epigenome in rhesus macaques

Background: Wildfire smoke is responsible for around 20% of all particulate emissions in the U.S. and affects millions of people worldwide. Children are especially vulnerable, as ambient air pollution exposure during early childhood is associated with reduced lung function. Most studies, however, have focused on the short-term impacts of wildfire smoke exposures. We aimed to identify long-term baseline epigenetic changes associated with early-life exposure to wildfire smoke. We collected nasal epithelium samples for whole genome bisulfite sequencing (WGBS) from two groups of adult female rhesus macaques: one group born just before the 2008 California wildfire season and exposed to wildfire smoke during early-life (n = 8), and the other group born in 2009 with no wildfire smoke exposure during early-life (n = 14). RNA-sequencing was also performed on a subset of these samples. Results: We identified 3370 differentially methylated regions (DMRs) (difference in methylation >= 5% and empirical p < 0.05) and 1 differentially expressed gene (FLOT2) (FDR < 0.05, fold of change >= 1.2). The DMRs were annotated to genes significantly enriched for synaptogenesis signaling, protein kinase A signaling, and a variety of immune processes, and some DMRs significantly correlated with gene expression differences. DMRs were also significantly enriched within regions of bivalent chromatin (top odds ratio = 1.46, q-value < 3 x 10-6) that often silence key developmental genes while keeping them poised for activation in pluripotent cells. Conclusions: These data suggest that early-life exposure to wildfire smoke leads to long-term changes in the methylome over genes impacting the nervous and immune systems, but follow-up studies will be required to test whether these changes influence transcription following an immune/respiratory challenge.

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The Neurobiology of Pain

The Oxford Handbook of the Neurobiology of Pain ◽

10.1093/oxfordhb/9780190860509.013.24 ◽

2019 ◽

pp. 387-414

Author(s):

Maria Fitzgerald ◽

Michael W. Salter

Keyword(s):

Early Life ◽

Pain Perception ◽

Long Term Effects ◽

Male And Female ◽

Functional Changes ◽

Pain Pathways ◽

Developmental Age ◽

Short And Long Term ◽

Age And Sex

The influence of development and sex on pain perception has long been recognized but only recently has it become clear that this is due to specific differences in underlying pain neurobiology. This chapter summarizes the evidence for mechanistic differences in male and female pain biology and for functional changes in pain pathways through infancy, adolescence, and adulthood. It describes how both developmental age and sex determine peripheral nociception, spinal and brainstem processing, brain networks, and neuroimmune pathways in pain. Finally, the chapter discusses emerging evidence for interactions between sex and development and the importance of sex in the short- and long-term effects of early life pain.

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Long term effects of early life stress on HPA circuit in rodent models

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2020.111125 ◽

2021 ◽

Vol 521 ◽

pp. 111125

Author(s):

Lucy Babicola ◽

Rossella Ventura ◽

Sebastian Luca D'Addario ◽

Donald Ielpo ◽

Diego Andolina ◽

...

Keyword(s):

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Rodent Models ◽

Long Term Effects

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Long-term effects of early life stress on the brain monoamines level in the rats

Neurophysiologie Clinique ◽

10.1016/j.neucli.2012.11.035 ◽

2013 ◽

Vol 43 (1) ◽

pp. 79

Author(s):

R. Ghalamghash ◽

H.Z. Mammedov ◽

H. Ashayeri ◽

A. Hosseini

Keyword(s):

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Long Term Effects ◽

Brain Monoamines ◽

The Brain

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Long-term effects of early pain and injury

Oxford Textbook of Pediatric Pain ◽

10.1093/med/9780198818762.003.0003 ◽

2021 ◽

pp. 21-37

Author(s):

Orla Moriarty ◽

Suellen M. Walker

Keyword(s):

Nervous System ◽

Early Life ◽

Tissue Injury ◽

Afferent Input ◽

Laboratory Studies ◽

Long Term Effects ◽

Nociceptive Pathways ◽

Noxious Stimuli ◽

Underlying Mechanisms

Nociceptive pathways are functional following birth, and acute responses to noxious stimuli have been documented from early in development in clinical and laboratory studies. The ability of noxious afferent input to alter the level of sensitivity of nociceptive pathways in the adult nervous system, with, for example, the development of central sensitization, is well established. However, the developing nervous system has additional susceptibilities to alterations in neural activity, and pain in early life may produce effects not seen following the same input at older ages. As a result, early tissue injury may lead to persistent changes in somatosensory processing and altered sensitivity to future noxious stimuli. Furthermore, there is increasing evidence that neonatal pain can result in long-term changes in cognitive and affective behavior. Effects of pain in early life are superimposed on a highly plastic developing system, and long-term outcomes vary depending on the type and severity of the injury, and on the evaluation methods used. Laboratory studies allow evaluation of different injuries, potential confounding factors, underlying mechanisms, and potential analgesic modulation.

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Developmental conditions modulate DNA methylation at the glucocorticoid receptor gene with cascading effects on expression and corticosterone levels in zebra finches

Scientific Reports ◽

10.1038/s41598-019-52203-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Blanca Jimeno ◽

Michaela Hau ◽

Elena Gómez-Díaz ◽

Simon Verhulst

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Glucocorticoid Receptor ◽

Early Life ◽

Receptor Gene ◽

Regulatory Region ◽

Long Term Effects ◽

Glucocorticoid Receptor Gene ◽

Developmental Conditions

Abstract Developmental conditions can impact the adult phenotype via epigenetic changes that modulate gene expression. In mammals, methylation of the glucocorticoid receptor gene Nr3c1 has been implicated as mediator of long-term effects of developmental conditions, but this evidence is limited to humans and rodents, and few studies have simultaneously tested for associations between DNA methylation, gene expression and phenotype. Adverse environmental conditions during early life (large natal brood size) or adulthood (high foraging costs) exert multiple long-term phenotypic effects in zebra finches, and we here test for effects of these manipulations on DNA methylation and expression of the Nr3c1 gene in blood. Having been reared in a large brood induced higher DNA methylation of the Nr3c1 regulatory region in adulthood, and this effect persisted over years. Nr3c1 expression was negatively correlated with methylation at 2 out of 8 CpG sites, and was lower in hard foraging conditions, despite foraging conditions having no effect on Nr3c1 methylation at our target region. Nr3c1 expression also correlated with glucocorticoid traits: higher expression level was associated with lower plasma baseline corticosterone concentrations and enhanced corticosterone reactivity. Our results suggest that methylation of the Nr3c1 regulatory region can contribute to the mechanisms underlying the emergence of long-term effects of developmental conditions in birds, but in our system current adversity dominated over early life experiences with respect to receptor expression.

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