The Signature of Maternal Rearing in the Methylome in Rhesus Macaque Prefrontal Cortex and T Cells

Abstract

Early life adversity is associated with a broad scope of life-long health and behavioral disorders. Particularly critical is the role of the mother. A possible mechanism is that these effects are mediated by “epigenetic” mechanisms. Studies in rodents suggest a causal relationship between early life adversity and changes in DNA methylation in several “candidate genes” in the brain. This study examines whether randomized differential rearing (maternal versus surrogate-peer rearing) of rhesus macaques is associated with differential methylation in early adulthood. The data presented here shows that differential rearing leads to differential DNA methylation in both prefrontal cortex and T cells. These differentially methylated promoters tend to cluster both by chromosomal region as well as by gene function. The broad impact of maternal rearing on DNA methylation in both the brain and T cells supports the hypothesis that the response to early-life adversity is system-wide and genome-wide and persists to adulthood. Our data also points to the feasibility of studying the impact of the social environment in peripheral T cells DNA methylation.

Genetic and early environmental influences on the serotonin system: consequences for brain development and risk for psychopathology

“…160 Such studies could be interpreted as the human equivalent of cross-fostering experiments with rats 136 and monkeys. 161 Finally, 5-HT has been implicated in a wide variety of psycho pathologies. Similar genetic variations and similar adversities have been linked to a wide variety of psychiatric disorders.…”

Folgen früher Traumatisierung aus neurobiologischer Sicht

“…Mittlerweile liegen erste Hinweise vor, dass sich leicht zu gewinnende periphere Zellen zur Untersuchung epigenetischer Folgen von Umwelteinflüs-sen eignen. Provençal et al (2012) konnten z. B. zeigen, dass Rhesusaffen, die getrennt von ihrer Mutter aufwuchsen, nicht nur im präfrontalen Kortex, sondern auch in peripheren T-Zellen Veränderungen in der DNA-Methylierung aufwiesen.…”

The dynamic epigenome and its implications for behavioral interventions: a role for epigenetics to inform disorder prevention and health promotion

“…The parent risk-taking behavior triggers change in methylation in his offspring that results in a risk-taking behavior in the child. Intervention could happen either by protecting the child from parental risk-taking behavior, thus preventing the development of risk-taking behavior in the child or using epigenetic therapy or behavioral therapy later in life to reverse the methylation state responsible for a risk-taking behavior ESSAY hypothesis that the response to maternal care is not limited to one tissue or one brain region but that it is system wide as well as genome wide [26]. The data are consistent with the idea that the phenotypic impact of early life adversity is not limited to the brain and involves other tissues such as the immune system [27].…”