Researchers in the United States have pinpointed a gene on the X chromosome that fuels inflammation in the female brain. This discovery offers new insight into why women are more prone to neurological conditions such as Alzheimer’s disease and multiple sclerosis.
A team at the University of California, Los Angeles (UCLA) conducted the study. It explains that females possess two X chromosomes, while males have only one. As a result, females experience a ‘double dose’ of inflammation.
Researchers believe this heightened immune activity significantly contributes to ageing and disorders such as Alzheimer’s and multiple sclerosis.
Using a mouse model of multiple sclerosis, scientists identified the gene Kdm6a, which triggers inflammation in microglia, the brain’s immune cells.
The researchers deactivated Kdm6a and its related protein. This reduced symptoms resembling multiple sclerosis and associated brain damage in female mice. The findings were published in Science Translational Medicine.
Lead author Dr Rhonda Voskuhl, director of the Multiple Sclerosis Programme at UCLA Health, stated, “Multiple sclerosis and Alzheimer’s disease each affect women more often than men, about two to three times as often. Also, two-thirds of healthy women have ‘brain fog’ during menopause. These new findings explain why and point to a new treatment to target this.”
The researchers further showed that genetically ‘knocking out’ Kdm6a in brain immune cells caused inflammatory molecules to revert from an active to a resting state.
The researchers also performed a pharmacological ‘knockdown’ of the protein produced by this gene. They used metformin, a drug commonly prescribed for diabetes.
These interventions showed strong positive effects in female mice but had minimal impact on males, Dr Voskuhl noted.
“This is consistent with there being ‘more to block’ in females due to having two copies of the X-linked gene,” Voskuhl stated. “It’s also why females are more likely to get multiple sclerosis and Alzheimer’s disease than males. This has implications for the clinic. Women may respond differently to metformin treatment than men.”
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