【Animal Modeling】-Age-related memory loss is reduced in mice

  Colombian scientists have uncovered new details about how natural hormones promote memory in aging mice, laying the foundation for people to avoid this form of memory loss. A study of Columbia rats revealed new details about how natural bone hormones restore memory loss in the aging brain. The discovery of these hormones called osteocalcin has inspired further research on the basic molecular mechanisms of memory and how to manipulate these mechanisms to improve them. The research also provides new insights to understand how lifestyle changes that affect the body (such as exercise) have a positive effect on the brain.

  The results of these studies led by Dr. Eric Kandel, the Nobel Prize winner, are reported today by Cell Reports researchers at Columbia University.

  "Almost everyone has experienced age-related memory loss, so it is very important to understand the cause and find ways to reduce its effects," said Professor of Brain Science Fog. Dr. Kandel said. Mortimer B. Zuckerman MindBrain Institute for Behavioral Research, co-director of Columbia University. "Through today's research, we have not only learned in detail how age-related memory loss occurs in the brain, but also how osteocalcin interacts with the main proteins in the brain to enhance memory. I have shown it. "

  points to another angle. For many years, when asked what we want to explore and how the body of the elderly acts and reverses the brain of the elderly, memory loss has been regarded as a disease. Later, scientists began to realize that not all forms of memory loss are the same. Alzheimer's disease changes the brain with age-related memory loss in many ways. This is a mild but common memory impairment. Alzheimer's disease and age-related memory loss both affect the hippocampus, but the brain's learning and memory headquarters are targeted at a completely different area within this area. Dr. Kandel, a senior researcher at the Howard Hughes Medical Institute, said: "Alzheimer's disease develops in the entorhinal cortex of the hippocampus." In contrast, age-related memory loss begins in the dentate gyrus of the hippocampus itself. area.

  In 2013, Dr. Kandel and his team discovered another difference between the two diseases. The bAp48 protein deficiency is an important part of age-related memory loss, but not an important part of Alzheimer's disease. Studies have shown that in mice and humans, the level of RbAp48 decreases with age. The researchers found that this reduction could be offset; when they artificially increased RbAp48 in the dentate gyrus of older mice, the animal’s memory improved.

  In 2017, researchers discovered another way to improve mouse memory. In collaboration with Professor Paul A. Marks of Columbia University Urban Medical Center and Gerald Carsenti, chair of the Department of Genetics and Development, he discovered that the infusion of osteocalcin, which is usually released from bone cells, has a positive effect on memory.

  Today’s research associates osteocalcin with RbAp48. This shows that the main motivation for improving memory is the interaction between these molecules. In a series of molecular and behavioral experiments, the researchers found that RbAp48 can regulate the expression levels of BDNF and GPR158. Both are controlled by osteocalcin. This series of events seems to be very important. If the function of RbAp48 is impaired, the infusion of osteocalcin will not affect animal memory. Osteocalcin requires RbAp48 to initiate this process. This complex molecular signal sequence is completely different from the sequence associated with Alzheimer's disease. Dr. Kandel said: "This is the clearest evidence that age-related memory loss and Alzheimer's disease are different diseases." These findings also provide other evidence that may be to avoid or treat age-related The best way to lose memory. Research on mice by Dr. Carsenti's team has shown that moderate exercise (such as walking) induces the release of osteocalcin in the body. Dr. Kandel suggested that osteocalcin may enter the brain over time and encounter RbAp48. Ultimately, this can have long-term positive effects on memory and the brain.

  "This concept points to another task line we want to explore, that is, how does the body of the elderly act on the brain of the elderly and reverse it?" Dr. Kandel asked. "Our latest findings are almost certainly not all."