New Discoveries About How Males and Females Respond to Stress Differently at the Molecular Level

Ligia Assumpcao Papale, Ph.D. - Brain & Behavior Research Expert on Depression
Ligia Assumpcao Papale, Ph.D.

New animal studies have revealed significant differences in how male and female brains respond to stress on a molecular level. The findings may help researchers identify biological factors that underlie differences in how men and women are affected by psychiatric disorders, such as the higher prevalence of depression and anxiety among women.  

The research, published August 26 in the journal Neurobiology of Disease, focused on how stress affects patterns of a chemical called 5-hydroxymethylcytosine (5hmC), which cells incorporate into their DNA to increase or decrease the activity of specific genes. The presence of 5hmC can also shift how the cell reads a gene, so that a slightly different form of protein can be manufactured using the same genetic template.

In times of stress, gene activity changes dramatically. Cells can quickly ramp up the activity of hundreds of genes while quieting hundreds more. These changes appear to be regulated in part by the addition or removal of 5hmC at thousands of spots throughout the genome.

Hundreds of genes in the brain react to stress differently in male and female mice. Tweet >

Earlier this year, a team of researchers led by Reid Alisch, Ph.D., at the University of Wisconsin, Madison, mapped all of the places on DNA where 5hmC markers have appeared or disappeared an hour after male mice are exposed to stress. They focused on cells in the hippocampus, a part of the brain that plays a key role in learning and memory. The stress-induced 5hmC changes that they detected affected more than 600 genes.

For the new study, the same team of scientists, which included 2014 Young Investigator Ligia Assumpcao Papale, Ph.D., at the University of Wisconsin, Madison, 2010 Young Investigator Qi Zhang, Ph.D., at the University of Nebraska, Lincoln, and 2013 Independent Investigator Peng Jin, Ph.D., at Emory University School of Medicine, mapped stress-induced 5hmC changes in the hippocampus of female mice.

This time, the researchers found 363 genes whose 5hmC patterns were altered by stress, some of which have also been implicated in stress-related psychiatric disorders. While some genes underwent stress-induced 5hmC changes in both males and females, the researchers identified more than 700 genes that were affected differently in the two sexes.

These different responses to acute stress could point researchers toward biological processes that influence how males and females cope with stress or their susceptibility to stress-related
mental illness, mostly commonly depression and anxiety. Understanding these processes could help researchers develop more effective ways, possibly sex-specific ways, to treat or prevent such conditions.

TAKEAWAY: Hundreds of genes in the brain’s hippocampus gain or lose an activity-regulating marker called 5hmC when an animal is exposed to stress. The genes affected by these stress-induced changes differ significantly in males and females.