London – Scientists have successfully reversed age-related memory loss in mice which could lead to preventing memory loss in people as they age.
The Cambridge and Leeds university research teams say changes in the extracellular matrix of the brain lead to loss of memory with ageing.
They say it is now possible to reverse these using genetic treatments.
Recent evidence has emerged of the role of perineuronal nets (PNNs) in neuroplasticity — the ability of the brain to learn and adapt — and to make memories.
PNNs are cartilage-like structures that mostly surround inhibitory neurons in the brain.
Their main function is to control the level of plasticity in the brain. They appear at around five years old in humans and turn off the period of enhanced plasticity during which the connections in the brain are optimised.
Then, plasticity is partially turned off, making the brain more efficient but less plastic.
PNNs contain compounds known as chondroitin sulphates. Some of these, such as chondroitin 4-sulphate, inhibit the action of the networks, inhibiting neuroplasticity; others, such as chondroitin 6-sulphate, promote neuroplasticity.
As people age, the balance of the compounds change and as levels of chondroitin 6-sulphate decrease, the ability to learn and form new memories change, leading to age-related memory decline.
Researchers investigated whether manipulating the chondroitin sulphate composition of the PNNs might restore neuroplasticity and alleviate age-related memory deficits.
The researchers saw remarkable results when they treated ageing mice with their treatment.
The memory and ability to learn were restored to levels they would not have seen since the mice were much younger.
To 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 to mimic the changes of ageing.
Although the study was on 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.
The researchers identified a potential drug, licensed for human use, that can be taken by mouth and inhibits the formation of PNNs.
When this compound is given to mice and rats it can restore memory in ageing and also improves recovery in spinal cord injury.
The approach taken by the team, using viral vectors to deliver the treatment, is increasingly being used to treat human neurological conditions.
