When the brain cells of the female mice express only the maternal X chromosome, their memory and their cognitive capacities deteriorate more quickly.
- In female mice with an active maternal X chromosome, cognitive deficits are accompanied by an acceleration of biological aging of the hippocampus, a key center for learning and memory.
- In cells, some genes are completely silenced on maternal X chromosomes.
- Activation by a specific technique of genes on maternal X chromosomes improves cognition in rodents.
Women are born with two X chromosomes and inherit one of each parent. During development, one of the X chromosomes is inactivated randomly in each cell of their body. Thus, certain cells only use maternal X chromosome, others than paternal X chromosome. Hypotheses, advanced by scientists, suggest that X chromosomes could help explain the gender differences in cognition, verbal memory or risk of brain disease. “Since the X chromosome is enriched with brain -related genes, it has become very important for us to know which roles it could play in the aging of the brain”, said Samira Abdulai-Saikuresearcher at the University of California in San Francisco (United States).
An accelerated aging of the hippocampus in mice with an active maternal x chromosome
In a new study, she therefore, with her team, wanted to determine if the origin of the mother or father chromosome was dispersed in the cells, because during the formation of eggs and sperm, chemical marks are added to certain genes on chromosomes. These brands differ depending on whether the chromosome comes from the mother (ovum) or the father (sperm). They have an impact on the genes that are activated when each chromosome is used in cells.
For the needs of the work, the authors have raised female mice so that they express either maternal X chromosomes, or a mixture of maternal and paternal x chromosomes. “The asymmetry of the X chromosome is frequent in humans, and there are certainly women who have levels of maternal X chromosomes much or lower than others, just by chance.” According to the results, published in the journal Naturethe female mice having only an active maternal X chromosome presented a lower memory and learning capacities as they age. In the brain of these mice, the maternal X chromosome has accelerated the biological aging of the hippocampus, an area of the crucial brain for learning and memory.
Genoes reduced to silence on maternal x chromosomes
A further analysis on brain cells has shown that some genes were completely silenced on maternal X chromosomes, but not on paternal X chromosomes. “It may be that this genetic expression model is in fact very beneficial for brain development, but that there is a compromise later in life”, explained the researchers. When the silence genes have been activated using specific technology, animals have become smarter at advanced age.
In the conclusions, the team indicates that understanding how the mother’s chromosome X alters brain functions could make it possible to better understand the heterogeneity of cognitive health in women and the derived routes of the X chromosome which protect against cognitive deficits and brain aging.
