What they found: Scientists at Cambridge University recently conducted a study, where they successfully reversed age-related memory loss in mice, giving hope for the development of potential future treatments for the problem.
How it works: As we age, the balance of compounds in PNN’s (Perineuronal nets) changes, effecting our ability to learn and form new memories, therefore leading to age-related memory decline.
Perineuronal nets (PNN’s) main function is to control the level of plasticity in the brain (the ability of the brain to learn and adapt). They appear at the age of around five in humans, and turn off during the period where brain plasticity connections are the most optimised. The brain therefore becomes more efficient but less plastic as we get older.
Certain compounds within PNN’s are responsible for inhibiting or promoting neuroplasticity. As we age, the balance of these compounds changes, and as levels of a compound called chondroitin 6-sulphate decrease, so our ability to learn and form new memories changes. This therefore triggers age-related memory decline.
The Study: The researchers investigated whether manipulating the composition of the chondroitin sulphate would restore neuroplasticity and alleviate age-related memory loss. The study involved 20 month old mice - considered very old for a mouse - who had memory deficits, and compared them to six month old mice.
For the study, researchers tested to see whether the mice recognised an object, by placing it at the start of a Y shaped maze, leaving it to explore the two identical objects at either end. After a short while, one object was changed, whilst the other object remained the same. Again, the mouse was placed at the start of the maze and left to explore the two objects. The researchers measured the amount of time the mouse spent exploring each object to see if it had remembered the object from the previous task. They found the older mice were much less likely to remember the object.
The team then treated the ageing mice using a virus, which is capable of restoring the amount of 6-sulphate chondroitin sulphates to the PNNs. They found that this completely restored memory in the older mice, to a level similar to that seen in the younger mice.
Other findings - To further explore the role of chondroitin 6-sulphate in memory loss, the researchers bred mice that had been genetically-manipulated such that they were only able to produce low levels of the compound, which mimics the changes of ageing in the brain. At just 11 weeks the mice showed signs of premature memory loss, however when they increased levels of the sulphate using the virus treatment they has used during their previous test. Using this treatment they found that the viral vector treatment had restored their memory and plasticity levels similar to healthy mice.
Professor James Fawcett from the John van Geest Centre for Brain Repair at the University of Cambridge said: “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. This suggests that it may be possible to prevent humans from developing memory loss in old age.”
Already the team have identified an oral drug which is licensed for human use, that has been shown to restore memory in ageing and improve recovery in spinal and cord injury in mice and rats. The researchers are currently investigating whether it might help alleviate memory loss in animal models of Alzheimer’s disease.
Another benefit is that the viral vector treatment is increasingly being used to treat human neurological conditions. You can see more on the research here: repairing damage caused by glaucoma and dementia.
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