Female rats in study handle stress better


Female rodents handle stress much better than males, which may hint at why women who are socially isolated seem better able to survive than lonely men, a pioneering University of Chicago research team is reporting today.

The difference in the female lab rats' responses may stem from the demands of motherhood, the researchers speculated. The idea is that mothers who can fend off stress and injury can better protect their young.

The study used 120 rats to document the long-lasting effect that three months of isolation -- the equivalent of chronic social stress -- and one 30-minute episode of acute physical stress had on the function of the rodents' immune systems.

The researchers measured what is known as the inflammatory response, the body's initial, fundamental immune reaction to bacteria, viruses and other invaders. Two or three weeks after being subjected to isolation and the brief period of acute physical stress, male rats showed a markedly slower inflammatory response than female rats when injected with a foreign body.

The response of the female rats was "staggeringly stronger," the authors wrote in their paper, which appears in the American Journal of Physiology.

"The study reinforces a growing body of evidence on health disparities between men and women, and may shed light on why socially isolated men are more vulnerable to disease and death than isolated women," said Gretchen Hermes, one of the authors.

Senior author Martha McClintock noted that the inflammatory response "not only is at the heart of auto-immune diseases but also is involved in cancer, heart disease, infectious disease -- just a whole variety of problems."

"Showing the effects of social isolation on the fundamental immune process has a lot of clinical implications," she said.

McClintock, a psychology professor and director of the Institute for Mind and Biology at the University of Chicago, specializes in determining how social interactions and individual beliefs regulate gene expression, affecting health and sickness.

She and her colleagues are most famous for finding the first conclusive scientific evidence of human pheromones -- airborne chemical signals that can't be detected with the five senses but apparently influence how we think, feel and behave.

McClintock studies tough Norway rats, which have evolved into survivors, instead of their weaker, genetically inbred cousins. Common sewer rats are a particularly social species that live in large colonies of closely spaced burrows with cooperative grooming, feeding and rearing of offspring.

The study covered three months, a significant portion of the rat's life span, and showed the lasting effects of an acutely stressful event superimposed on the chronic social condition of isolation.

"We stressed the animals for just 30 minutes by putting them in a plastic restraint tube that mimics the collapse of their burrow," McClintock said. "Two weeks later, we tested them and found huge sex differences in response to that very brief physical stressor."

Among the males, the episode of acute stress further delayed the inflammatory response when they were exposed to a foreign substance. "But in the females, it actually compensated for the effects of isolation. It had a positive enhancing effect on the immune system," McClintock said.

The results dovetail with studies that have found that rats are more likely to give birth to female offspring than male offspring in times of stress, McClintock said, as it suggests males are less likely to survive under stressful circumstances.

It is not clear why females heal more quickly than males under stress, but the authors said it might be a protection that evolved as females tried to protect their offspring.

"While lactating, maternal rats become highly aggressive toward intruders and predators and are at high risk for wounding, particularly from neck bites," the paper noted.

So it makes evolutionary sense for females to respond to an immediate stressor by enhancing the inflammatory response and healing more quickly, McClintock said.

Another possibility is that males and females experience stress differently, the study said. If females perceive the restraint as more traumatic, they may react more strongly to the introduction of the foreign body and produce a stronger immune reaction.

"I think probably the most striking thing are the dramatic sex differences in the enduring effects of a brief stress," McClintock said. "If I were to link the study to what's in the news right now, there are studies of differences in heart disease in men and women. We used to think they were the same disease, but now we know the nature of the inflammation is very different.

McClintock said she hoped the study would be an important contribution in the understanding of sex differences of disease "but, specifically, disease as it occurs in the context of real social and psychological life."

Peter Gorner writes for the Chicago Tribune.

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