Age-related memory loss is widely believed to begin around the age of 60, but some research suggests that memory and other mental declines may commonly occur decades earlier. Making conscious efforts to boost your brain function is crucial in preventing age-related memory loss. Now, a new study gives hope in restoring this loss. Scientists at Cambridge and Leeds say they have successfully reversed age-related memory loss in mice.
Their study is published in the journal Molecular Psychiatry in a paper titled, “Chondroitin 6-sulphate is required for neuroplasticity and memory in aging.”
The researchers demonstrated that changes in the extracellular matrix of the brain lead to loss of memory with aging, but introducing genetic treatments may reverse this loss.
“Perineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory,” wrote the researchers. “Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. 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 main function of PNNs is to control the level of plasticity in the brain. As we age, the balance of the compounds, chondroitin sulphate, changes, along with our ability to learn and form new memories changes, leading to age-related memory decline.
The researchers observed 20-month-old mice and compared their deficits in their memory to six-month-old mice. “We first confirmed that aged mice (20 months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated,” wrote the researchers.
Then the researchers treated the aging mice using a viral vector, capable of reconstituting the amount of 6-sulphate chondroitin sulphates to the PNNs. They discovered that the memory in the older mice was restored to a similar level seen in younger mice.
“We saw remarkable results when we treated the aging mice with this treatment,” explained Jessica Kwok, PhD, from the School of Biomedical Sciences at the University of Leeds. “The memory and ability to learn were restored to levels they would not have seen since they were much younger.”
The researchers then bred mice that had been genetically modified to produce low levels of the compound to mimic the changes of aging. They observed premature memory loss in the genetically modified mice, but observed restored memory and plasticity after increasing levels of chondroitin 6-sulphate using the viral vector.
“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,” added James Fawcett, PhD, professor, John van Geest Centre for Brain Repair at the University of Cambridge.
The team of researchers has identified a potential drug, licensed for human use, that can be taken by mouth and inhibits the formation of PNNs. Currently, they are investigating whether it might help alleviate memory loss in animal models of Alzheimer’s disease.