Researchers identify protein linking exercise to brain health

US researchers said Friday that a protein that is increased during endurance exercise may help boost brain health. Researchers from the Dana-Farber Cancer Institute and Harvard Medical School found that the protein, called FNDC5, turned on genes that promote brain health and encourage the growth of new nerves involved in learning and memory, when given to non- exercising mice. The findings, reported in the journal Cell Metabolism, help explain the well-known capacity of endurance exercise to improve cognitive function, particularly in older people. If the protein can be made in a stable form and developed into a drug, it might lead to improved therapies for cognitive decline in older people and slow the toll of neurodegenerative diseases such as Alzheimer's and Parkinson's, according to the researchers. The researchers previously reported that the protein is produced by muscular exertion and is released into the bloodstream as a variant called irisin. In the new study, they found that mice voluntarily running on a wheel for 30 days will have increased activity of a metabolic regulatory molecule in muscles, which spurred a rise in FNDC5 protein. The increase of FNDC5 in turn boosted the expression of a brain- health protein, called BDNF, in the hippocampus, a part of the brain involved in learning and memory, the researchers said. Having shown that FNDC5 is a molecular link between exercise and increased BDNF in the brain, the scientists looked into whether artificially increasing FNDC5 in the absence of exercise would have the same effect. They used a harmless virus to deliver the protein to mice through the bloodstream, in hopes the FNDC5 could reach the brain and raise BDNF activity. Seven days later, they examined the mouse brains and observed a significant increase in BDNF in the hippocampus. "What is exciting is that a natural substance can be given in the bloodstream that can mimic some of the effects of endurance exercise on the brain," study author Bruce Spiegelman, of Dana- Farber and Harvard Medical School, said in a statement. However, the researchers said they aren't sure whether the protein that got into the brain is FNDC5 itself, or irisin, or perhaps another variant of the protein. Spiegelman added that further research is needed to determine whether giving FNDC5 actually improves cognitive function in other animals.