Science Sub-Journal: Genes are related to the cognitive flexibility of the elderly

Researchers have found that among these people with strong cognitive flexibility, the level of education and the length of time engaged in intellectual stimulation activities are factors that help prevent dementia

Researchers have observed this link between MEF2 and cognitive flexibility in humans and mice

Li-hui Tsai, director of the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology (MIT), said: “People are increasingly realizing that there are some elastic factors that can protect brain function.

Cai is the senior author of the study, which was published today in Science Translational Medicine

Protective effects

A large number of studies have shown that environmental stimulation has a certain protective effect on neurodegeneration

The MIT team tried to figure out how these environmental factors affect the brain at the neuron level

MEF2 is a transcription factor, which was initially considered to be an important factor for myocardial development, but was later discovered to play a role in neuronal function and neurodevelopment

Many of these genes code for ion channels, and ion channels control the excitability of neurons, or the ease with which neurons emit electrical impulses

In order to study the cognitive flexibility of mice, the researchers compared two groups of mice.

When the researchers knocked out the MEF2 gene in the frontal cortex, the mice could not benefit from the rich environment, and their neurons became extremely excited

"This is particularly exciting because it shows that MEF2 plays a role in determining the overall cognitive potential of responses to environmental variables," Raju said

The researchers then investigated whether MEF2 can reverse some of the symptoms of cognitive impairment in a mouse model.

"Many human studies and mouse model studies on neurodegeneration have shown that neurons become over-excited in the early stages of disease progression," Raju said

Improve resilience

The results of the study show that enhancing the activity of MEF2 helps prevent dementia; however, the researchers say that since MEF2 also affects other types of cells and cellular processes, more research is needed to ensure that activation does not produce undesirable side effects

The MIT research team now hopes to further investigate how MEF2 is activated by exposure to a rich environment

Raju said: "You can imagine a more targeted treatment by identifying a subset or class of effectors that are essential for inducing resilience and neuroprotection

The research was funded by the Glenn Center for Aging Biology, the National Institute of Aging, the Cure Alzheimer's Disease Fund, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development
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Journal Reference :

1. Scarlett J.
   Barker, Ravikiran M.
   Raju, Noah EP Milman, Jun Wang, Jose Davila-Velderrain, Fatima Gunter-Rahman, Cameron C.
   Parro, P.
   Lorenzo Bozzelli, Fatema Abdurrob, Karim Abdelaal, David A.
   Bennett, Manolis Kellis , Li-Huei Tsai.
   MEF2 is a key regulator of cognitive potential and confers resilience to neurodegeneration .
   Science Translational Medicine , 2021; 13 (618) DOI: 10.
   1126/scitranslmed.
   abd7695