A study in mice has revealed details of how a hormone called osteocalcin, that naturally occurs in bones, reverses memory loss in the aging brain. Furthermore, the study done by scientists at Columbia University, suggests that lifestyle changes such as exercise could positively affect the brain through this hormone. The findings were published today in Cell Reports.
While once thought to be a singular disorder, it is now apparent that memory loss is a collection of disorders, not all created equal. Alzheimer’s disease changes the brain in different ways than age-related memory loss. Both affect the hippocampus, but each targets a distinct area within that region.
In 2013, the Columbia research team discovered another difference between the two disorders. A deficiency in the RbAp48 protein contributes to age-related memory loss, but not Alzheimer’s. RbAp48 levels decline with age in humans and mice, but when the researchers artificially increased the protein in aging mice, the animals’ memory improved. In a later study, the researchers found that infusions of osteocalcin also had a positive effect on memory.
In the current study, the researchers performed a series of molecular and behavior experiments to analyze the connection between RbAp48 and osteocalcin. They found that RbAp48 controls the expression levels of BDNF and GPR158, which are both regulated by osteocalcin. If RbAp48 function is inhibited, osteocalcin infusions have no effect on animal memory indicating it needs RbAp48 to start its memory-enhancing process.
The findings provide further supporting evidence to age-related memory loss and Alzheimer’s being separate diseases. They also provide evidence that exercise could help alleviate age-related memory loss. Studies in mice have shown moderate exercise, such as walking, triggers release of osteocalcin in the body.
Image: These are dentate gyrus from a mouse with GPR158 protein knocked down. Image courtesy of Stylianos Kosmidis/Kandel lab/Columbia's Zuckerman Institute.