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Scientists Reverse Memory Loss Caused by Aging in Mice

An already-licensed drug could do the same for humans.

Scientists at the University of Cambridge have found the cause of aging-related memory loss in mice. During the course of their research, they discovered that memory loss could even be reversed in old mice in laboratory experiments. 

Scientists have been looking for the causes of age-induced memory loss. They found one in the scaffolding that holds the brain's neurons in place. Called perineuronal nets (PNNs), these cartilage-like structures surround the neurons in our brain. Intriguingly, these nets appear at the age of five in humans after a period of neuroplasticity during which the brain learns, adapts, and makes memories.

The role of the PNNs is to reduce the plasticity in the brain, making it less capable of creating new memories while increasing the efficiency of the brain in performing regular tasks. 

This is why learning becomes difficult as we age — PNNs are working to make the brain more and more efficient. This is done by a PNN constituent called chondroitin 4-sulfate. 

The human brain is not fixed, however. It wants to make new memories as well. So, it uses a similar compound, called chondroitin 6-sulfate, that improves the ability to make memories and learn new things.

As we age, the brain maintains a balance of these two compounds, but chondroitin 4-sulfate increases, reducing our ability to make new memories, like where the glasses are kept or if we took our medication.

Professor James Fawcett and his team of researchers at the John van Geest Centre for Brain Repair at the University of Cambridge teamed up with Dr. Jessica Kwok and her team at the School of Biomedical Sciences at the University of Leeds to investigate if changing levels of chondroitin sulfates could be used to improve memory-making in old age. 

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For their study, they used 20-month-old mice, considered quite advanced in age for mice. They then subjected them to different tests to observe their memory-making capacities, comparing them to those of six-month-old mice. As was expected, the six-month mice performed better at memory-making tasks. The researchers then used a virus to infect the mice's PNNs and increase the levels of chondroitin 6-sulfate in them. 

 “We saw remarkable results when we treated the aging mice with this treatment," said Dr. Kwok at the University of Leeds. "The memory and ability to learn were restored to levels they would not have seen since they were much younger." The results were published in Molecular Psychiatry

Professor Fawcett at The University of Cambridge said that the molecules and structures in the human and rodent brains are the same. So, the same mechanism could operate in humans too. 

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But, we would not need to infect human PNNs with a virus. An orally taken drug that has been licensed for human uses for other conditions can perform this task. Researchers have used it in mice studies before and now believe it could also reverse aging-related memory loss. The team is currently working to see if the treatment can work for Alzheimer's disease as well. 

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