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Dentate gyrus of the brain of a mouse. Credit: Stylianos Kosmidis / Kandel Laboratory / Columbia Zuckerman Institute
Columbia scientists have revealed new details on how a natural hormone can boost memory in aging mice, paving the way for the elimination of this form of memory loss in humans.
A Columbia study in mice revealed new details on how a natural bone hormone reverses memory loss in the aging brain. These findings on the hormone, called osteocalcin, will spur new investigations into the molecular mechanisms underlying memory – and how these mechanisms can be manipulated to improve them. The research also provides new insights into how lifestyle changes that affect the body, such as exercise, could positively affect the brain.
These findings were reported today by a team of researchers from Colombia, led by Nobel laureate Eric R. Kandel, MD, Cell reports.
"Almost everyone will experience age-related memory loss in their lifetime. It is therefore extremely important to understand its causes and find ways to mitigate them, "said Dr. Kandel, a professor at the University and professor of brain sciences at Kavli. co-director of Mortimer B. Zuckerman of the British Mortimer Brain Behavior Institute B. "With today's study, we are not only developing a detailed understanding of the origin of aging-related memory loss. she also showed how osteocalcin interacts with key brain proteins to stimulate memory. "
This notion refers to another area of research that we are eager to explore: how does the aging body affect the aging brain and how can it be reversed?
For many years, memory loss has been treated as a singular disorder. So scientists have begun to realize that not all forms of memory loss are created equal.
Alzheimer's disease alters the brain in different ways than age-related memory loss, a less serious memory disorder, but much more common. While Alzheimer's and age-related memory loss affects the hippocampus, the seat of the brain for learning and memory, each targets a completely different area in this region.
"Alzheimer's disease starts in a part of the brain called the entorhinal cortex, which lies at the foot of the hippocampus," said Dr. Kandel, also a principal investigator at the Howard Hughes Medical Institute. "Age-related memory loss, on the other hand, starts in the hippocampus itself, in a region called the dentate gyrus."
In 2013, Dr. Kandel and his team discovered another difference between the two disorders: RbAp48 protein deficiency contributes significantly to age-related memory loss but not to Alzheimer's disease. Research has shown that RbAp48 levels decrease with age, in mice and in humans. The researchers found that this decline could be neutralized. when they artificially increased RbAp48 in the dentate gyrus of aging mice, animal memory improved.
In 2017, researchers found another way to improve the memory of mice. In collaboration with Gerard Karsenty, MD, Ph.D., professor and Paul A. Marks Chair in the Department of Genetics and Development at Columbia University's Irving Medical Center, scientists have discovered that osteocalcin infusions , hormone normally released by bone cells, had a positive effect on memory. .
Today's study links osteocalcin to RbAp48, suggesting that the main factor improving memory is the interaction between these molecules. In a series of molecular and behavioral experiments, the team discovered that RbAp48 controlled the expression levels of BDNF and GPR158, two proteins regulated by osteocalcin. This chain of events seems to be critical; if the function of RbAp48 is inhibited, osteocalcin infusions have no effect on the animal's memory. Osteocalcin needs RbAp48 to start the process.
This complex sequence of molecular signals is totally different from that associated with Alzheimer's disease. "This is the clearest evidence to date that age-related memory loss and Alzheimer's disease are distinct diseases," said Dr. Kandel.
These findings also provide additional evidence for what might be the best way to counteract, or even treat, age-related memory loss in people: exercise. Studies in mice by Dr. Karsenty's team have shown that moderate exercise, such as walking, triggers the release of osteocalcin into the body. Dr. Kandel suggests that over time, osteocalcin may end up in the brain where it meets RbAp48. Ultimately, this could have a long-term positive effect on memory and the brain.
"This notion refers to another area of research that we are eager to explore: how does the aging body affect the aging brain and how can it be reversed? not all history. They are only the beginning. "
This article has been republished from documents provided by Columbia University in New York City. Note: Content may have changed for length and content. For more information, please contact the cited source.
Reference:
Kosmidis, S., Polyzos, A., Harvey, L., Youssef, C., A., Dranovsky, A. and Kandel, E. (2018). RbAp48 is an essential component of GPR158 / OCN signaling and improves age-related memory loss. Cell reports, 25(4). doi: 10.1016 / j.celrep.2018.09.077
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