Science Sub-Journal: Environment + MEF2 transcription factor is related to the "cognitive flexibility" of the elderly

These findings may help explain why some people with rich lives are not prone to Alzheimer's disease

With age, many people will develop Alzheimer's or other forms of dementia

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-Huei 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

Tsai is the senior author of the study, which was published in the journal Science Translational Medicine on November 3, 2021

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

Use the chip to detect the epigenome, and receive the detailed technical information of the Arraystar epitranscriptome chip

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

Research results show that enhancing MEF2 activity helps prevent dementia

The MIT research team now hopes to further investigate how MEF2 is activated by exposure to a rich environment
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In addition to the ion channels explored in this study, they also plan to study the effects of other genes controlled by MEF2
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This type of research helps reveal additional goals for drug therapy
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Raju said: "You can expect a more targeted treatment by identifying a subset of transcription factors that are essential for inducing resilience and neuroprotection
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"

“MEF2 is a key regulator of cognitive potential and confers resilience to neurodegeneration” by 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 and Li-Huei Tsai, 3 November 2021, Science Translational Medicine .

DOI: 10.
1126/scitranslmed.
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