A study in mice has revealed new details of how a naturally occurring bone hormone reverses memory loss in the aging brain. These findings about the hormone, called osteocalcin, stand to spur further investigations into the molecular machinery that underlies memory -- and how that machinery can be manipulated to improve it. The research published in Cell Reports, also lends new insight into how lifestyle changes that affect the body, such as exercise, could positively affect the brain.
"Nearly everyone will experience age-related memory loss in their lifetimes, so it is incredibly important to understand its causes and identify ways to mitigate it," said the senior author and Nobel laurate. "With today's study, we are not only building a detailed understanding of how age-related memory loss originates in the brain, we've shown how osteocalcin interacts with key proteins in the brain to boost memory."
For many years, memory loss was treated as a singular disorder. Then scientists began to realize that not all forms of memory loss are created equal.
Alzheimer's disease changes the brain in different ways than does age-related memory loss, a milder, though far more common, memory disorder. While both Alzheimer's and age-related memory loss affect the hippocampus, the brain's headquarters for learning and memory, each targets a completely differently area within that region.
"Alzheimer's disease begins in a part of the brain called the entorhinal cortex, which lies at the foot of the hippocampus," said the senior author. "Age-related memory loss, by contrast, begins within the hippocampus itself, in a region called the dentate gyrus."
In 2013, the team discovered another difference between the two disorders: A deficiency in the RbAp48 protein is a significant contributor to age-related memory loss but not Alzheimer's. Research has shown that RbAp48 levels decline with age, both in mice and in people. This decline can be counteracted, the researchers found; when they artificially increased RbAp48 in the dentate gyrus of aging mice, the animals' memories improved.
In 2017, the researchers found another way to improve the memories of mice. The scientists found that infusions of osteocalcin, a hormone normally released by bone cells, had a positive effect on memory.
This study connects osteocalcin and RbAp48, suggesting that the key driver of the memory improvements lay in the interplay between these molecules. In a series of molecular and behavioral experiments, the team found that RbAp48 controls the expression levels of BDNF and GPR158, two proteins regulated from osteocalcin. This chain of events appears to be critical; if RbAp48 function is inhibited, osteocalcin infusions have no effect on the animals' memory. Osteocalcin needs RbAp48 to kick start the process.
This complex sequence of molecular signals is entirely different from those associated with Alzheimer's disease. "This is the clearest evidence yet that age-related memory loss and Alzheimer's are distinct diseases," said the senior author.
These findings also provide further evidence in favor of what may be the best way to stave off, or even treat, age-related memory loss in people: exercise. Studies in mice by the team have shown that moderate exercise, such as walking, triggers the release of osteocalcin in the body. The senior author proposes that, over time, osteocalcin may make its way to the brain, where it encounters RbAp48. Eventually, this could have a long-term, positive effect on memory and the brain.
https://zuckermaninstitute.columbia.edu/how-reverse-memory-loss-old-mice
https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31537-7
Old age and Alzheimer's memory loss are different!
- 1,127 views
- Added
Edited
Latest News
Men with gene mutations are…
By newseditor
Posted 17 May
B cell oxidative phosphoryl…
By newseditor
Posted 17 May
Human brain gene therapy us…
By newseditor
Posted 16 May
Small-molecular mimic of a…
By newseditor
Posted 16 May
Centromere structure and ch…
By newseditor
Posted 16 May
Other Top Stories
How fish brain responds to beta-amyloid challenge?
Read more
Delivering synthetic nanomaterial to prevent the scarring after hea…
Read more
Tooth enamel damage from mutation of a gene
Read more
Brain's emotional center contributes to eating for pleasure!
Read more
Disrupting protein-RNA interaction prevents neurotoxicity in ALS
Read more
Protocols
Breast cancer-on-chip for p…
By newseditor
Posted 16 May
Methods for making and obse…
By newseditor
Posted 15 May
Mime-seq 2.0: a method to s…
By newseditor
Posted 13 May
Improved detection of DNA r…
By newseditor
Posted 09 May
Single-cell adhesive profil…
By newseditor
Posted 07 May
Publications
Obesity-induced blood-brain…
By newseditor
Posted 18 May
CRISPR/Cas9 model of prosta…
By newseditor
Posted 17 May
Modulation of host immunity…
By newseditor
Posted 17 May
Variability in cell divisio…
By newseditor
Posted 17 May
Biallelic BORCS8 variants c…
By newseditor
Posted 17 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar