An intriguing new study from researchers in the United Kingdom is proposing an innovative method to treat age-related memory loss. The preclinical research shows memory decline in aging mice can be reversed by manipulating the composition of structures in the brain known as perineuronal nets.
Perineuronal nets (PNNs) are structures in the brain that envelop certain subsets of neurons, helping stabilize synaptic activity. They essentially put the brakes on the neuroplasticity seen in the first few years of life.
Although PNNs are vital to the effective functioning of a mature adult brain, by their very nature they also limit future neural plasticity and adaptability. A new wave of research is beginning to investigate ways to modulate PNNs in adult brains in the hope of treating a variety of diseases from diabetes to post-traumatic stress disorder (PTSD).
This new study arose out of research elucidating the role PNNs play in memory acquisition. Prior animal studies suggest that PNNs can become more inhibitory with age, disrupting the formation of new memories. So hypothetically, age-related memory loss could be reversed by modulating PNN function.
Chondroitin sulphates are chemicals that can either promote or inhibit the function of PNNs. Chondroitin 6-sulphate, for example, promotes neuroplasticity while chondroitin 4-sulphate does the opposite.
As we age the balance between these two chemicals changes, and chondroitin 6-sulphate levels decrease. It is this mechanism the researchers suspect plays a part in how PNNs influence age-related memory decline.
Exploring this hypothesis the researchers manipulated the chondroitin sulphate composition in old mice. Levels of chondroitin 6-sulphate in PNNs were restored and the results were impressive. Memory deficits in the older mice were restored to levels seen in their younger counterparts.
“We saw remarkable results when we treated the ageing mice with this treatment,” explains Jessica Kwok, a researcher from the University of Leeds working on the study. “The memory and ability to learn were restored to levels they would not have seen since they were much younger.”
The researchers then specifically engineered mouse models to produce low levels of chondroitin 6-sulphate. These animals showed very premature signs of age-related memory loss, affirming the role chondroitin 6-sulphate plays in memory. And, when these mice had their chondroitin 6-sulphate levels restored, their memory improved to that seen in young healthy animals.
What is exciting about this is that although our study was only in mice, the same mechanism should operate in humans
A drug, already developed and approved for use in humans, has been found to inhibit PNN formation and this is being tested in mouse models of Alzheimer’s disease.
James Fawcett, from the University of Cambridge, says a more focused therapy targeting chondroitin 6-sulphate in humans could hypothetically be an effective treatment to prevent age-related memory loss. While the researchers do stress it is very early days for the work, and these new findings have only been demonstrated in animal models at this point, Fawcett says the mechanisms should translate to humans.
“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,” says Fawcett. “This suggests that it may be possible to prevent humans from developing memory loss in old age.”
The new study was published in the journal Molecular Psychiatry.
Source: University of Cambridge
