Scientists from Cambridge and Leeds have successfully reversed memory loss linked to age in mice and say their discovery could lead to the development of treatments to prevent memory loss in people as they age.
In a study published today in Molecular Psychiatry, the team shows that changes in the brain’s extracellular matrix, “scaffolding” around nerve cells, lead to memory loss with aging, but that it is possible to reverse them using genetic treatments .
Recent evidence has emerged of the role of perineuronal networks (PNNs) in neuroplasticity, the ability of the brain to learn and adapt, and to create memories. PNNs are cartilage-like structures that primarily surround inhibitory neurons in the brain.
Their main function is to control the level of plasticity in the brain. They appear around the age of five in humans and deactivate the period of increased plasticity during which connections in the brain are optimized. Thus, plasticity is partially turned off, making the brain more efficient but less plastic.
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PNNs contain compounds known as chondroitin sulfates. Some of these, such as chondroitin 4-sulfate, inhibit the action of networks, inhibiting neuroplasticity; others, such as chondroitin 6-sulfate, promote neuroplasticity.
As we age, the balance of these compounds changes, and as chondroitin 6-sulfate levels decline, our ability to learn and form new memories changes, leading to age-related memory decline.
Researchers at the University of Cambridge and the University of Leeds investigated whether manipulating the chondroitin sulfate composition of PNNs could restore neuroplasticity and relieve age-related memory deficits.
To do this, the team examined 20-month-old mice, considered very old, and using a series of tests showed that the mice showed deficits in their memory compared to the six-month-old mice.
For example, one test involved seeing if the mice recognized an object. The mouse was positioned at the beginning of a Y-shaped maze and allowed to explore two identical objects at the ends of the two arms. After a while, the mouse was placed back into the maze, but this time one arm contained a new object, while the other contained a copy of the repeating object.
The researchers measured the amount of time the mouse spent exploring each object to see if it had remembered the object of the previous activity. Older mice were less likely to remember the object.