Groomed DNA handles threats: mothering styles alter rats' stress responses.

A rodent mother can't scold or praise her offspring, but her approach to mothering lays a genetic foundation for her pups' lifelong response to threats, neuroscientists have found.

Rats raised by moms who frequently lick and groom them undergo permanent changes in patterns of gene activity, leading to a penchant for exploratory behavior in stressful situations, say Michael J. Meaney and his colleagues at McGill University in Montreal.

In contrast, rats raised with little maternal contact end up with gene activity that fosters fearfulness in the face of stress, the researchers report in the August Nature Neuroscience. From an evolutionary perspective, having both behaviors in a population is beneficial.

"Early experience can have lifelong consequences on behavior, and [this new report] reveals the genetic scaffolding of this phenomenon to an unprecedented extent," remarks neuroscientist Robert Sapolsky of Stanford University.

Meaney's group previously showed that female rats express either a high- or a low-contact mothering style. Animals raised with lots of physical contact later react to stress by secreting small amounts of glucocorticoids, a class of stress hormones. These rats also possess large numbers of glucocorticoid receptors in an inner-brain structure called the hippocampus. Rats raised with little physical contact secrete large amounts of glucocorticoids when stressed and possess relatively few receptors for these hormones.

In another study, Meaney's group found that pups raised by doting mothers had high concentrations of a substance called nerve growth factor-inducible protein A (NGFI-A) in their hippocampi. It attaches to genes for glucocorticoid receptors, boosting those genes' capacity to regulate the hormone's secretion.

The researchers' new report shows how NGFI-A offers stress-fighting aid only to pampered rats. On the first day after birth, in all the rat pups, regulatory proteins inactivate NGFI-A's binding location on glucocorticoid-receptor genes. Over the next week, in rats raised with high-contact mothering, the concentration of these regulatory proteins decreases sufficiently to enable NGFI-A to do its job of boosting production of hormone receptors. These rats retain this genetic trait for life, the investigators say.

In contrast, the regulatory proteins in unpampered rats stay high, and the abundance of hormone receptors remains low.

Moreover, only high-contact animals displayed another biochemical change, according to Meaney's team. The change decreased the binding of histones to DNA, thereby letting NGFI-A attach and boost the activity of glucocorticoid-receptor genes.

The researchers also tested a drug that blocks the binding of histones to DNA. When they injected it into adult rats that had been raised by low-contact mothers, the scientists found that the animals responded to stress much as pampered animals do. These behaviors were reflected on the molecular level, in patterns of expression of stress hormones and receptors.

Whether differing styles by human mothers induce similar molecular changes in their offspring remains an open question.