Over 60 years ago, Selye1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly contradictory roles? How does stress influence the pathogenesis of disease, and what accounts for the variation in vulnerability to stress-related diseases among people with similar life experiences? How can stress-induced damage be quantified? These and many other questions still challenge investigators. This article reviews the long-term effect of the physiologic response to stress, which I refer to as allostatic load.2 Allostasis — the ability to achieve stability through change3 — . . .

/pdf/protective-and-damaging-effects-of-stress-mediators-34e0m747fy.pdf

Protective and Damaging Effects of Stress Mediators

Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.

/pdf/epigenetic-programming-by-maternal-behavior-nhsklwyk7o.pdf

Epigenetic programming by maternal behavior.

How we raise young children is one of today's most highly personalized and sharply politicized issues, in part because each of us can claim some level of "expertise." The debate has intensified as discoveries about our development-in the womb and in the first months and years-have reached the popular media. How can we use our burgeoning knowledge to assure the well-being of all young children, for their own sake as well as for the sake of our nation? Drawing from new findings, this book presents important conclusions about nature-versus-nurture, the impact of being born into a working family, the effect of politics on programs for children, the costs and benefits of intervention, and other issues. The committee issues a series of challenges to decision makers regarding the quality of child care, issues of racial and ethnic diversity, the integration of children's cognitive and emotional development, and more. Authoritative yet accessible, From Neurons to Neighborhoods presents the evidence about "brain wiring" and how kids learn to speak, think, and regulate their behavior. It examines the effect of the climate-family, child care, community-within which the child grows.

/pdf/from-neurons-to-neighborhoods-the-science-of-early-childhood-3bfl5g72ow.pdf

From Neurons to Neighborhoods: The Science of Early Childhood Development

Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.

Effects of stress throughout the lifespan on the brain, behaviour and cognition

▪ Abstract Socioeconomic status (SES) is one of the most widely studied constructs in the social sciences. Several ways of measuring SES have been proposed, but most include some quantification of family income, parental education, and occupational status. Research shows that SES is associated with a wide array of health, cognitive, and socioemotional outcomes in children, with effects beginning prior to birth and continuing into adulthood. A variety of mechanisms linking SES to child well-being have been proposed, with most involving differences in access to material and social resources or reactions to stress-inducing conditions by both the children themselves and their parents. For children, SES impacts well-being at multiple levels, including both family and neighborhood. Its effects are moderated by children's own characteristics, family characteristics, and external support systems.

Socioeconomic status and child development.

Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats. As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed reduced plasma adrenocorticotropic hormone and corticosterone responses to acute stress, increased hippocampal glucocorticoid receptor messenger RNA expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of hypothalamic corticotropin-releasing hormone messenger RNA. Each measure was significantly correlated with the frequency of maternal licking and grooming (all r 9s > −0.6). These findings suggest that maternal behavior serves to “program” hypothalamic-pituitary-adrenal responses to stress in the offspring.

http://science.sciencemag.org/content/sci/277/5332/1659.full.pdf

Maternal Care, Hippocampal Glucocorticoid Receptors, and Hypothalamic-Pituitary-Adrenal Responses to Stress

In the rat, variations in maternal care appear to influence the development of behavioral and endocrine responses to stress in the offspring. The results of cross-fostering studies reported here provide evidence for (i) a causal relationship between maternal behavior and stress reactivity in the offspring and (ii) the transmission of such individual differences in maternal behavior from one generation of females to the next. Moreover, an environmental manipulation imposed during early development that alters maternal behavior can then affect the pattern of transmission in subsequent generations. Taken together, these findings indicate that variations in maternal care can serve as the basis for a nongenomic behavioral transmission of individual differences in stress reactivity across generations.

https://science.sciencemag.org/content/sci/286/5442/1155.full.pdf

Nongenomic Transmission Across Generations of Maternal Behavior and Stress Responses in the Rat

The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, (ii) increased α2 adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus. The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus ceruleus to the forebrain structures. Considering the importance of the amygdala, notably the anxiogenic influence of CRH projections from the amygdala to the locus ceruleus, as well as the anxiolytic actions of benzodiazepines, for the expression of behavioral responses to stress, these findings suggest that maternal care during infancy serves to “program” behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.

https://www.pnas.org/content/pnas/95/9/5335.full.pdf

Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat

We report that variations in maternal care in the rat promote hippocampal synaptogenesis and spatial learning and memory through systems known to mediate experience-dependent neural development. Thus, the offspring of mothers that show high levels of pup licking and grooming and arched-back nursing showed increased expression of NMDA receptor subunit and brain-derived neurotrophic factor (BDNF) mRNA, increased cholinergic innervation of the hippocampus and enhanced spatial learning and memory. A cross-fostering study provided evidence for a direct relationship between maternal behavior and hippocampal development, although not all neonates were equally sensitive to variations in maternal care.

Darlene D. Francis

Papers

Maternal Care, Hippocampal Glucocorticoid Receptors, and Hypothalamic-Pituitary-Adrenal Responses to Stress

Nongenomic Transmission Across Generations of Maternal Behavior and Stress Responses in the Rat

Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat

Maternal care, hippocampal synaptogenesis and cognitive development in rats.

Variations in maternal care in the rat as a mediating influence for the effects of environment on development.