Researchers have found that boosting levels of osteocalcin, a hormone produced by bone cells, can reverse age-related memory loss. A team from Columbia University Medical Center also found a receptor for osteocalcin in the brain, which could help create a new way to treat age-related cognitive decline. These findings appear in today's Journal of Experimental Medicine.
In previous studies, osteocalcin was found to play a role in memory and decline in levels during early adulthood. This lead to the study leader, Gerard Karsenty, M.D., Ph.D., Paul A. Marks Professor and Chair, department of genetics & development, and their laboratory to ask, "Could memory loss be reversed by restoring this hormone back to youthful levels? The answer, at least in mice, is yes, suggesting that we've opened a new avenue of research into the regulation of behavior by peripheral hormones."
Karsenty's group, in collaboration with the laboratory of Eric Kandel, M.D., University Professor and Kavli Professor of Brain Science at Columbia University and a contributor to this study, conducted several experiments to evaluate osteocalcin's role in age-related memory loss. In their experiments, scientists gave aged mice either infusions of osteocalcin, osteocalcin-rich plasma from young mice, or plasma from young osteocalcin-deficient mice with added osteocalcin. In all cases, they found that the aged mice showed memory improvement. In addition, they used anti-osteocalcin antibodies to deplete the hormone from the plasma of young mice, which reduced their performance on memory tests.
The researchers then determined that osteocalcin binds to a receptor called Gpr158 that is abundant in neurons of the CA3 region of the hippocampus. This was confirmed by inactivating hippocampal Gpr158 in mice and subsequently giving them infusions of osteocalcin, which failed to improve their performance on memory tests.
The researchers did not observe any toxic effects from giving the mice osteocalcin. "It's a natural part of our body, so it should be safe," said Karsenty. However, of course, more research needs to be completed before moving into clinical use for humans.
Image: Washington Irving (Own work) [Public domain], via Wikimedia Commons