Epigenetic Programming of Stress Responses through Variations in Maternal Care

Abstract

Early life experiences shape an individual's physical and mental health across the lifespan. Not surprisingly, an upbringing that is associated with adversity can produce detrimental effects on health. A central theme that arises from studies in human and nonhuman species is that the effects of adversity are mediated by the interactions between a mother and her young. In this review we describe some of the long-term effects of maternal care on the offspring and we focus on the impact of naturally occurring variations in the behavior of female rats. Of particular interest are mothers that engage in high or low amounts of licking/grooming (LG) and arched-back nursing (ABN) of their pups, but do so within the normal range for this species. Such variations in LG-ABN can alter the function of the hypothalamic-pituitary-adrenal (HPA) axis, and cognitive and emotional development by directly affecting the underlying neural mechanisms. At the heart of these mechanisms is gene expression. By studying the hippocampal glucocorticoid receptor gene, we have identified that maternal care regulates its expression by changing two processes: the acetylation of histones H3-K9, and the methylation of the NGFI-A consensus sequence on the exon 1(7) promoter. Sustained "maternal effects" appear elsewhere in biology, including plants, insects, and lizards, and may have evolved to program advantages in the environments that the offspring will likely face as adults. Given the importance of early life and parent-child interactions to later behavior, prevention and intervention programs should target this critical phase of development.

Influence of housing variables on the development of stress-sensitive behaviors in the rat

“…6). Evidence supporting direct maternal programming of offspring stress physiology is supported by studies in which an increase in early maternal care has been demonstrated to decrease stress reactivity and anxiety proles of Long Evans rats later in adulthood [26,28,32]. Ostensibly, our results are consistent with this literature and a 'maternal mediation' model, in which maternal investment serves as a link between environments and offspring.…”

“…A robust literature highlights the importance of early life environmental variables that inuence stress responsivity in adult offspring, primarily using the laboratory rat as a model [1,28,[36][37][38][39]. One environmental variable demonstrated to inuence offspring development is the material on which rodents are housed [40].…”

“…For example, alterations in early post-natal maternal care in the laboratory rat can program the developing HPA-neuroendocrine pathways and behavioral fearfulness when rodents reach adulthood [26][27][28][29]. These effects persist throughout the life of the animal and alter risk for stress-related disease [2,4,30].…”

Childhood and Later Life Stressors and Increased Inflammatory Gene Expression at Older ages

“…It has been suggested that physiological adaptations in response to adversity during development may contribute to "environmental programming" of the stress response via alterations in DNA methylation, histone acetylation, and transcription factor binding (Meaney & Szyf, 2005). Such effects have been well documented in animal models which demonstrate that elevated hypothalamic-pituitaryadrenal axis (HPA) activation in adulthood can be traced back to alterations in chromatin structure that resulted from a stressful early-life environment (Meaney et al, 2007;Weaver et al, 2004;Fish et al, 2004).…”

Genetic Predictions of Future Dangerousness: Is there a Blueprint for Violence?

“…Rat pups regularly licked and groomed by their mothers instead grow up to be calm and curious. 222 Closer to home, geneticists investigated the claim that a gene called 5-HTT is associated with depression and suicide. 223 When people experience very stressful events, they found, those who carry this gene are more likely to suffer from depression than those with the "healthy" variant.…”