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Scientists reverse effects of aging in the brains of mice 

 

When we age, our brains lose their flexibility, impacting our ability to learn, remember and adapt. 

But researchers have shown that they can rejuvenate the plasticity of the brain: The brain’s ability to change throughout life. 

By manipulating a single gene in mice, researchers were able to trigger the shift in the brain’s visual cortex. 

The findings could be used as a potential target for treatments to recover the human brain’s youthful potential after a stroke, or even after age-related decline. 

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Over-expressing a single gene called Arc rejuvenates the visual cortex of middle-aged mice, making them as plastic as young mice. This image shows cells in the visual cortex in which Arc has been manipulated. The bright, fluorescent spots are cells that have excess Arc 

Over-expressing a single gene called Arc rejuvenates the visual cortex of middle-aged mice, making them as plastic as young mice. This image shows cells in the visual cortex in which Arc has been manipulated. The bright, fluorescent spots are cells that have excess Arc 

Over-expressing a single gene called Arc rejuvenates the visual cortex of middle-aged mice, making them as plastic as young mice. This image shows cells in the visual cortex in which Arc has been manipulated. The bright, fluorescent spots are cells that have excess Arc 

The research, published in the journal PNAS, could potentially lead to treatments for reducing age-related cognitive decline. 

‘It’s exciting because it suggests that by just manipulating one gene in adult brains, we can boost brain plasticity,’ says lead investigator researcher Dr Jason Shepherd, Assistant Professor of Neurobiology and Anatomy at the University of Utah Health. 

‘This has implications for potentially reducing normal cognitive decline with aging, or boosting recovery from brain injury after stroke or traumatic brain injury,’ he says.

Researchers showed that they can rejuvenate the plasticity of the brain - the brain's ability to change throughout life - in the visual cortex of mice. By manipulating a single gene, researchers were able to trigger the shift - and it could be used to develop human treatments 

Researchers showed that they can rejuvenate the plasticity of the brain - the brain's ability to change throughout life - in the visual cortex of mice. By manipulating a single gene, researchers were able to trigger the shift - and it could be used to develop human treatments 

Researchers showed that they can rejuvenate the plasticity of the brain – the brain’s ability to change throughout life – in the visual cortex of mice. By manipulating a single gene, researchers were able to trigger the shift – and it could be used to develop human treatments 

Additional research will need to be done to determine whether plasticity in humans and mice is regulated in the same way. 

The brain changes dramatically over time, for example, a ‘critical window’ of brain plasticity explains why certain eye conditions such as lazy eye can be corrected during early childhood, but not later in life. 

This phenomenon has led researchers to ask what keeps this window open, and once it’s shut, can plasticity be restored? 

WHAT THEY FOUND  

The brain changes dramatically over time, for example, a ‘critical window’ of brain plasticity explains why certain eye conditions such as eye can be corrected during early childhood, but not later in life. 

Earlier research by Dr Jason Shepherd, Assistant Professor of Neurobiology and Anatomy at University of Utah Health, and Dr Mark Bear, a professor at MIT and co-author of the current study, showed that this critical window never opens in mice lacking a gene called Arc.

In an experiment where the researchers temporarily closed a single eye of a young mouse for a few days, the visual cortex was deprived of normal input, and the neurons’ electrophysiological response to visual experience changed. 

By contrast, however, mice without the Arc gene cannot adapt to this new experience in the same way.

In another set of experiments, the researcher tested mice that have a strong supply of Arc throughout life. 

At middle-age, the mice responded to visual deprivation in the same was as juveniles. 

This showed that by prolonging Arc’s availability, the window for plasticity stayed open for longer. 

In a second set of experiments, the researchers used viruses to deliver Arc to middle-aged mice – after the critical window had closed. 

After this, these older mice responded to visual deprivation just as a younger one would. 

 Even though the window had shut, Arc allowed it to re-open.

Earlier research by Dr Shepherd and Dr Mark Bear, a professor at MIT and co-author of the current study, showed that this critical window never opens in mice lacking a gene called Arc. 

In an experiment where the researchers temporarily closed a single eye of a young mouse for a few days, the visual cortex was deprived of normal input, and the neurons’ electrophysiological response to visual experience changed. 

By contrast, mice without the Arc gene cannot adapt to this new experience in the same way.

‘Given our previous studies, we wondered whether Arc is essential for controlling the critical period of plasticity during normal brain development,’ says Dr Shepherd. 

The researchers suspected that if there is no visual plasticity without the Arc gene, then the gene may play a role in keeping the critical window open. 

To test this idea, the researchers conducted a new investigation, finding that in the mouse visual cortex, Arc rises and fall in parallel with visual plasticity.

Both Arc and visual plasticity peal in teenage mice, and fall sharply by middle-age, which suggests they are linked. 

The researchers further tested this connection in two ways.

First, in collaboration with co-author Dr Harohiko Bito at the University of Tokyo, they tested mice that have a strong supply of Arc throughout life. 

At middle-age, the mice responded to visual deprivation in the same was as juveniles. 

This showed that by prolonging Arc’s availability, the window for plasticity stayed open for longer. 

But manipulating Arc is not the first treatment to prolong plasticity. 

Chronically treating mice with an antidepressant, fluoxetine, and raising them in a stimulating environment with toys and plenty of social interaction, are other factors that also prolong brain plasticity. 

In a second set of experiments, the researchers used viruses to deliver Arc to middle-aged mice – after the critical window had closed. 

After this, these older mice responded to visual deprivation just as a younger one would. 

Manipulating Arc is not the first treatment to prolong plasticity. Chronically treating mice with an antidepressant, fluoxetine, and raising them in a stimulating environment with toys and plenty of social interaction, are other factors that have been shown to prolong brain plasticity

Manipulating Arc is not the first treatment to prolong plasticity. Chronically treating mice with an antidepressant, fluoxetine, and raising them in a stimulating environment with toys and plenty of social interaction, are other factors that have been shown to prolong brain plasticity

Manipulating Arc is not the first treatment to prolong plasticity. Chronically treating mice with an antidepressant, fluoxetine, and raising them in a stimulating environment with toys and plenty of social interaction, are other factors that have been shown to prolong brain plasticity

Even though the window had shut, Arc allowed it to re-open. 

‘It was incredible to see that in adult mice, who have gone through normal development and aging, simply overexpressing Arc with a virus restored plasticity,’ says co-first author Kyle Jenks, a graduate student in Dr Shepherd’s lab.

Currently, the prevailing idea of how plasticity declines is that as the brain develops, ‘inhibitory neurons mature and become stronger, however, Dr Shepherd explains that he believes their findings add a new dimension for how critical learning periods are regulated. 

‘Increased inhibition in the brain makes it harder to express activity-dependent genes, like Arc, in response to experience or learning,’ Dr Shepherd says.

‘And that leads to decreased brain plasticity.’

Normally, Arc is rapidly activated in response to stimuli and is involved in shuttling neurotransmitter receptors out of synapses that neurons use to communicate with one another. 

According to the researchers, additional research will need to be done to understand precisely how manipulating Arc boosts plasticity.

Whether Arc is involved in regulating the plasticity of other brain functions mediated by other brain structures, such as learning, memory, or repair, remains to be tested but will be examined in the future, says Dr Shepherd.

 

 

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