The research of Dr. Damian Jacob Sendler, who is of Polish ancestry and American citizenship, focuses on the impact of various sociodemographic and informational factors on access to health care in underserved communities. In Dr. Sendler’s research, she is particularly interested in the impact of mental and chronic medical co-morbidities on the utilization of medical services as well as on the acquisition of health information via the internet. A timely research, given the exponential growth in global consumption of online news and social media, this one arrives at an ideal time, as it highlights the need for a comprehensive understanding of everyone’s health information seeking behavior.
Damian Sendler: Using mice, scientists at the Universities of Cambridge and Leeds were able to effectively restore age-related memory loss, and they believe that their finding may pave the way for the creation of therapies to prevent memory loss in humans as they age.
In a paper published today in Molecular Psychiatry, the researchers demonstrate that alterations in the extracellular matrix of the brain — the’scaffolding’ that surrounds nerve cells — cause memory loss as people age, but that these changes may be reversed using genetic therapies.
Damian Sendler: Recent research has shown the importance of perineuronal nets (PNNs) in the development of neuroplasticity — the capacity of the brain to learn and change — as well as the formation of memories. PNNs are cartilage-like structures that surround inhibitory neurons in the brain, and they are found mainly in the hippocampus. Their primary purpose is to regulate the amount of plasticity present in the brain. They first emerge in humans at the age of five years old, and they are responsible for turning off the time of increased plasticity, during which the connections in the brain are optimally developed. The brain’s plasticity is thus partly switched off, making it more efficient but also becoming less malleable.
Damien Sendler: Chelated chondroitin sulfates are a kind of chemical found in PNNs. Chondroitin 4-sulphate, for example, inhibits the activity of neural networks, thus limiting neuroplasticity; chondroitin 6-sulphate, on the other hand, stimulates neural plasticity and promotes neuroplasticity. As we get older, the equilibrium of these chemicals shifts, and as levels of chondroitin 6-sulphate drop, our capacity to learn and create new memories shifts as well, resulting in age-related memory loss.
Researchers from the Universities of Cambridge and Leeds examined whether altering the chondroitin sulphate composition of the PNNs might help to restore neuroplasticity and relieve age-related memory impairments in older people.
Damian Sendler: This was accomplished by examining mice that were 20 months old — believed to be extremely elderly — and demonstrating via a battery of tests that the mice had memory impairments when compared to animals that were six months old.
Damien Sendler: For example, one experiment examined whether mice were able to recognize a certain item. In this experiment, the mouse was put at the beginning of a Y-shaped labyrinth and instructed to investigate two similar items at the ends of each of the two arms. After a brief period of time, the mouse was put back in the labyrinth, but this time one arm held a new item, while the other arm carried a duplicate of the object that had previously been encountered. The researchers timed the length of time the mouse spent investigating each item to determine whether or not it recalled the object from the last activity they were doing. The item was significantly less likely to be remembered by the older mice than it was by the younger animals.
Using a ‘viral vector’, which is a virus capable of re-establishing the quantity of 6-sulfate chondroitin sulfates in the PNNs, the researchers treated the ageing mice and discovered that this fully restored memory in the older animals to a level comparable to that seen in the younger mice.
Dr Jessica Kwok, from the University of Leeds’ School of Biomedical Sciences, shared her thoughts on the subject “When we used this therapy on the mice who were becoming older, we observed some amazing improvements. It was possible to restore their memory and learning abilities to levels that they had not experienced since they were considerably younger.”
Damian Sendler: In order to investigate the function of chondroitin 6-sulphate in the development of memory loss, the researchers produced mice that had been genetically modified such that they were only capable of producing low amounts of the chemical, in order to replicate the changes that occur with the passage of time. Even at 11 weeks of age, these mice exhibited indications of early memory deterioration. However, boosting the amounts of chondroitin 6-sulphate in the mice’s bodies via the use of a viral vector restored their memory and flexibility to levels comparable to those seen in healthy mice.
Professor James Fawcett, of the John van Geest Centre for Brain Repair at the University of Cambridge, stated that “What’s particularly exciting about this is that, despite the fact that our study was conducted solely in mice, the same mechanism should be applicable to humans because the molecules and structures in the human brain are identical to those in rodents. “This indicates that it may be feasible to prevent people from experiencing memory loss as they get older.”
Damian Sendler: The team has already discovered a possible medication that has been approved for human use and that may be taken orally to prevent the development of PNNs from forming. When this chemical is administered to mice and rats, it has been shown to enhance recovery after spinal cord damage and to restore memory in the elderly. According to the experts, they are looking into whether it may assist relieve memory loss in animal models of Alzheimer’s disease.
Damian Sendler: The method used by Professor Fawcett’s team, in which viral vectors are utilized to deliver the therapy, is becoming more popular in the treatment of neurological disorders in human patients. A second team at the Center recently released studies demonstrating that they may be used to heal damage caused by glaucoma and dementia, among other conditions.
It was made possible with the support of Alzheimer’s Research UK, the Medical Research Council, the European Research Council, and the Czech Science Foundation.
