Medical

Restoring brain plasticity may hold key to reversing age-related cognitive decline

Restoring brain plasticity may...
Evidence suggests age-related cognitive decline is not caused by brain cells dying but rather a simple reduction in plasticity, which could be reversed
Evidence suggests age-related cognitive decline is not caused by brain cells dying but rather a simple reduction in plasticity, which could be reversed
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Evidence suggests age-related cognitive decline is not caused by brain cells dying but rather a simple reduction in plasticity, which could be reversed
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Evidence suggests age-related cognitive decline is not caused by brain cells dying but rather a simple reduction in plasticity, which could be reversed

Normal aging is commonly associated with a variety of mild sensory and cognitive declines. Separate to any acute dementia-related disease, this average age-related brain decline has been commonly thought to be caused by a slow reduction in the total number of brain cells. However, a new study from MIT's Picower Institute for Learning and Memory suggests that a reduction in the plasticity of certain neurons could be the fundamental cause of normal age-related cognitive decline.

The new experiments focused on inhibitory interneurons in the visual cortex of mice. Aging of inhibitory interneurons is a little studied area and these neurons are hypothesized to be crucial to brain plasticity.

"Despite common belief, loss of neurons due to cell death is quite limited during normal aging and unlikely to account for age-related functional impairments," the researchers write, in a statement accompanying the new study. "Rather it seems that structural alterations in neuronal morphology and synaptic connections are features most consistently correlated with brain age, and may be considered as the potential physical basis for the age-related decline."

The study first tracked the growth and structure of inhibitory interneurons in mice at several key ages. Mice generally live for about 24 months, and while a three-month-old mouse is considered mature, an 18-month-old mouse would be the equivalent of a senior citizen. The initial research found that there was no significant decline in the number of inhibitory brain cells as the animal aged.

What the researchers did find though was a decline in several plasticity markers beginning around the age of six months. The growth of dendrites, the branches that connect neurons, was seen to progressively slow down between the ages of three and 18 months. This inability for a brain to dynamically remodel itself is a key feature in reduced plasticity.

Another form of plasticity measured is called stimulus-selective response potentiation (SRP). This measurement examines the neuronal process underlying visual recognition memory. When our brains are youthful and plastic they respond potently to visual stimuli but SRP measurements show these responses decline with age. In the new mouse study SRP measurements were noted as robust at three months but barely evident by nine months.

The final part of the study set out to see if these reductions in plasticity could be reversed. The researchers utilized a drug called fluoxetine, better known as Prozac, as previous work found it enhanced interneuron remodeling in younger mice. Interestingly, the mice treated with fluoxetine for at least six months, beginning at the age of three months, displayed significant improvements in all plasticity markers, including dendrite growth and SRP measurements.

"Our finding that fluoxetine treatment in aging mice can attenuate the concurrent age-related declines in interneuron structural and visual cortex functional plasticity suggests it could provide an important therapeutic approach towards mitigation of sensory and cognitive deficits associated with aging, provided it is initiated before severe network deterioration," the researchers write.

While the research offers a compelling new hypothesis behind normal age-related cognitive decline, the suggestion fluoxetine could be a realistic therapeutic agent is not especially practical. The common antidepressant is already not recommended for use in the elderly due to its side effects, and the drug would have to be administered for an extensive period of time from a relatively young age to have any effect. All this is also assuming the drug's actions are replicated in human subjects, which is something that would take years of complex clinical trials to prove.

Perhaps the most pragmatic outcome from this study is the finding that a decline in brain plasticity can potentially be reversed, meaning the kinds of age-related cognitive degeneration we just accept comes with getting older may in fact be something that can be modulated in the future.

The new research was published in the Journal of Neuroscience.

Source: Picower Institute for Learning and Memory

6 comments
judahis
Worthy science is that which challenges unproven assumptions. Thanks MIT.
Xaria
The question begs to be answered...do we truly know what we are doing? Just because one thing is seen to change doesn’t mean that reversing it is the answer! Humans are still woefully ignorant of how our own bodies work this requires much more study!
Username
Xaria, much more study is exactly what these people are doing.
ljaques
Finding cures for horrible diseases like Alzheimers and dementia is good. BUT, given the previous disastrous result of feeding anti-depressants to individuals, don't we have -enough- depressed school shooters? They're recruiting more from the elderly population? WTeverlovingF? Cruise the results of this and see if you think MIT is on the wrong path: https://www.google.com/search?q=serial+killers+prozac Scientists and doctors don't know enough about what's happening in our skulls now, and research into it is great, but using known bad drugs trying to reach different outcomes is a really, really bad idea, IMHO.
deacs
There is a US company that specializes in neural and synaptic protection and they've completed a phase 2 study which showed increased cognitive scores in moderate to severe patients who were not taking memantine drugs. They have recently started a confirmation trial with more patients, none of which will be on memantine which apparently interferes with the drugs affectiveness. Additional results should be known next summer. Their drug is bryostatin and the company has a website at neurotropebiosciences.com. It is an unique theory (brain plasticity, interneuron protection) but some are advancing similar research
Nik
Before taking any anti depressant drug, read the ''side effects.'' They are usually dangerous, unpleasant, long lasting, and may not be reversible. They are the real effects. Any benefits are usually the real side effects. As 'Big Pharma' in the USA has made itself immune from claims against it from any bad effects of its drugs, it can poison people with total impunity, and profit enormously from it. I have found that half a teaspoonful of ground cinnamon per day, with my morning yogurt, has noticeable beneficial effects on brain function. (I'm 74). I can recommend it to anyone of a similar age.