Cell-type-specific epigenetic effects of early life stress on the brain

Abstract

Early life stress (ELS) induces long-term phenotypic adaptations that contribute to increased vulnerability to a host of neuropsychiatric disorders. Epigenetic mechanisms, including DNA methylation, histone modifications and non-coding RNA, are a proposed link between environmental stressors, alterations in gene expression, and phenotypes. Epigenetic modifications play a primary role in shaping functional differences between cell types and can be modified by environmental perturbations, especially in early development. Together with contributions from genetic variation, epigenetic mechanisms orchestrate patterns of gene expression within specific cell types that contribute to phenotypic variation between individuals. To date, many studies have provided insights into epigenetic changes resulting from ELS. However, most of these studies have examined heterogenous brain tissue, despite evidence of cell-type-specific epigenetic modifications in phenotypes associated with ELS. In this review, we focus on rodent and human studies that have examined epigenetic modifications induced by ELS in select cell types isolated from the brain or associated with genes that have cell-type-restricted expression in neurons, microglia, astrocytes, and oligodendrocytes. Although significant challenges remain, future studies using these approaches can enable important mechanistic insight into the role of epigenetic variation in the effects of ELS on brain function.

The epigenetic legacy of ICU feeding and its consequences

“…Others include histone-modification and expression of noncoding RNAs (miRNA, lncRNA). Epigenetic involvement in the long-term legacy after critical illness appears plausible, as aberrant epigenetic changes have been linked to abnormal development and disease resulting from adverse environmental exposures/stressors [11][12][13][14][15][16].…”

“…Aberrant epigenetic changes have been linked to abnormal development and long-term disease resulting from adverse environmental exposures, such as early-life or other stress and inadequate nutrition [11][12][13][14][15][16]. Critical illness imposes extreme stress.…”

Genome editing in cotton: challenges and opportunities

“…The modification of genetic expression by dCas9 is a transient process, as it does not cause permanent modifications to the genomic DNA. However, specific and long-lasting modifications to genetic expression are possible through the fusion of epigenetic modifiers to dCas9 (Rahman and McGowan 2022). Several effector domains may be fused with dCas9 DBD to get various modifications in gene expression at different levels.…”

Remembering through the genome: the role of chromatin states in brain functions and diseases

“…Early life conditions such as stress before or after birth can have effects on physiology, behavior and cognition that can last until adulthood [78]. These effects have been associated with transcriptional and epigenetic changes in components of the hypothalamic-pituitary-adrenal (HPA) axis, neurotransmitter signaling and neuroimmune pathways in neuronal and glial cells in the brain [79][80][81][82][83]. For instance, chronic stress between postnatal day (PND) 10 and 17 in mice globally alters the level of H3K79me1/2 in nucleus accumbens (NAc) in the adult brain, a region involved in motivation and reward [12].…”