Researchers Restore Age-Related Memory Loss in Mice

Researchers Restore Age-Related Memory Loss in Mice

Progressive cognitive decline and memory loss are common as people age, which is why it is important to keep the brain active and take steps to boost brain function. Boosting brain function can help to slow and even prevent age-related memory loss and loss of cognitive function, but currently there are no treatments available that are effective at reversing these age-related declines.

Age-related memory loss is thought to start from the age of 60, although in some cases, decline in brain function can occur much earlier. Decline in brain function can greatly affect quality of life, but new research suggests that it may be possible to restore age-related memory loss. Researchers at the University of Cambridge and the University of Leeds claim to have successfully reversed age-related memory loss in mice and suggest it may also be possible to do so in humans.

The researchers showed that changes to the extracellular matrix of the brain related to aging can lead to memory loss, but genetic treatments could potentially be provided to reverse that memory loss.

The neuronal surface has chondroitin sulphate proteoglycan-containing structures called perineuronal nets (PNNs) which have been implicated in the control of neuroplasticity and memory. As people age, their ability to learn and create new memories changes, which leads to age-related memory decline.

“Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory,” explained the researchers. “Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice.”

The researchers studied 20-month-old mice to confirm they had memory and plasticity deficits. The researchers showed that when CSs were digested or PNNs were attenuated, the mice were able to retain or regain their cognitive ability. Following the study, the researchers explored he role C6S played in memory and neuroplasticity.

Aging mice were treated using a viral vector capable of reconstituting the amount of 6-sulphate chondroitin sulphates to the PNNs. After treatment, memory in the older mice and their ability to learn was restored to a level observed in younger mice.

Using mice that had been bred to produce low levels of C6S to mimic age-related changes, premature memory loss was observed in the mice. When C6S levels were increased using the viral vector, memory and plasticity increased.

“What is exciting about this is that although our study was only in mice, the same mechanism should operate in humans—the molecules and structures in the human brain are the same as those in rodents,” said James Fawcett, PhD, professor, John van Geest Centre for Brain Repair at the University of Cambridge. “This suggests that it may be possible to prevent humans from developing memory loss in old age.”

There is currently a drug on the market licensed for use in humans that can be taken orally which inhibits the formation of PNNs. The researchers are now investigating whether the drug could potentially be used to treat memory loss in animal models of Alzheimer’s disease.

You can read more about the study in the paper – Chondroitin 6-sulphate is required for neuroplasticity and memory in aging – which was recently published in the journal Molecular Psychiatry. DOI: 10.1038/s41380-021-01208-9