The second X chromosome which remains silent in women could cause female brain resilience during aging.
- Women have two X chromosomes. One of the two remains silent.
- A new study on mice shows that this silent X is starting to express certain genes from 65 years old.
- This would explain why the brain of women ages better than that of men.
Women have two X chromosomes, but one of them remains inactivated in part of the cells, called barr corpuscule. So far, researchers thought this silent chromosome remained in its corner without doing anything.
But a recent study by the University of California in San Francisco has revealed that it could be an essential element of much slower brain aging.
“The silent X in women is actually awakening later in life, which probably helps to slow down the cognitive decline”explains Dena Dubal, main author of the works which appeared on March 5 in the review Science Advances.
Brain: silent x chromosome expresses cerebral development genes
Wishing to determine whether the silent X chromosome played a role in the slower cognitive decline of women, scientists created hybrid female mice. Half of them had a silent x. They then measured genetic expression in the hippocampus, a key brain region for learning and memory that deteriorates with aging, in female mice of 20 months. Which corresponds to 65 years in humans.
The analyzes have shown that the X chromosome which was supposed to be silent, actually expressed twenty genes in several types of hippocampal cells of these elderly animals. “Many of them play a role in brain development, as well as in intellectual disability”specify the authors in their press release.
“We immediately thought that this could explain how the brain of women remains resilient to typical aging, because men would not have this additional X”adds Margaret Gadek, first author of the article.
The Silent PLP1 gene stimulates the brain
Secondly, scientists have more precisely studied the activity of one of the genes of the X chromosome activated during aging: the PLP1 gene. The latter is known to contribute to the construction of myelin, sheath which covers certain nerve fibers.
Elderly female rodents had more than PLP1 in the hippocampus than males. Which suggests for researchers that “The additional PLP1 of the second X chromosome made a difference”.
To verify that this gene could explain the resilience of the female brain, the team expressed it artificially in the hippocampus of female and male mouse. Result: the additional PLP1 stimulated the brain of both sexes, and all animals presented better results to learning and memory tests.
Research to slow down cognitive decline
After these discoveries, the team will now try to determine whether the second X could also be active in elderly women. Previous work suggests that this is a possibility. Indeed, an analysis of brain tissue taken from the elderly of both sexes, revealed that only women presented a high rate of PLP1 in a brain region similar to that of mice.
Researchers will also try to see if treatments could help amplify the activity of X chromosome genes as PLP1 to slow down the cognitive decline.
