Spending time on intellectually stimulating activities appears to activate a gene family known as MEF2, which controls a genetic program in the brain that promotes resistance to cognitive decline. That’s according to a new study using human datasets and mouse models, conducted by researchers at the Massachusetts Institute of Technology.
In two human datasets comprising slightly more than 1,000 people all together, the MIT team found that cognitive resilience was highly correlated with expression of MEF2 and many of the genes that it regulates. Many of those genes encode ion channels, which control a neuron’s excitability, or how easily it fires an electrical impulse. The researchers also found, from a single-cell RNA-sequencing study of human brain cells, that MEF2 appears to be most active in a subpopulation of excitatory neurons in the prefrontal cortex of resilient individuals.
To study cognitive resilience in mice, the researchers compared mice who were raised in cages with no toys, and mice placed in a more stimulating environment with a running wheel and toys that were swapped out every few days. As they found in the human study, MEF2 was more active in the brains of the mice exposed to the enriched environment. These mice also performed better in learning and memory tasks. When the researchers knocked out the gene for MEF2 in the frontal cortex, this blocked the mice’s ability to benefit from being raised in the enriched environment, and their neurons became abnormally excitable.
The findings suggest that enhancing the activity of MEF2 or its targets might protect against age-related dementia.
“It’s increasingly understood that there are resilience factors that can protect the function of the brain,” said Li-Huei Tsai, Ph.D., director of MIT’s Picower Institute for Learning and Memory, and the study’s lead author. “Understanding this resilience mechanism could be helpful when we think about therapeutic interventions or prevention of cognitive decline and neurodegeneration-associated dementia.”
Full findings ran in Science Translational Medicine.
