Busy feet, better memory. A hormone released by bone during exercise improves memory storage and retrieval in aged mice 鈥� and a new study into the way it operates has identified a protein that could form the basis of a treatment for age-related memory loss.
As we get older, the gearwheels that keep our body functioning 鈥� such as hormone secretion and cell regeneration 鈥� turn at a slower rate. For instance, a bone-building hormone called osteocalcin is produced at a reduced level as we age.
In their previous research, Eric Kandel and his colleagues at Columbia University in New York found osteocalcin also plays an important role in cognition 鈥� mice with osteocalcin deficiency showed symptoms of memory loss. They have also tied this memory loss to the activity of a gene called RbAp48, the activity of which increases in mice injected with osteocalcin.
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Now Kandel鈥檚 team has explored further. They injected 16-month-old mice 鈥� an equivalent of 70 in human years 鈥� with osteocalcin. Within 48 hours, the team found the mice had a 15 per cent increase in the expression of RbAp48 in their brains.
What鈥檚 more, old mice given the injection appeared to have fewer problems with memory than old mice that had not received the hormone jab.
For instance, when the researchers presented old mice with two objects, one of which they had seen and familiarised themselves with the previous day, osteocalcin-injected mouse gave more attention to the unfamiliar object. The researchers say this suggests the treated mice recognised and largely ignored the familiar object. By contrast, untreated mice apparently failed to recognise the object they had seen the previous day and explored it almost as if it was a novel object.
Digging deeper, the researchers discovered that RbAp48 controls the expression of a protein called GPR158, which osteocalcin must bind to in order to pass along its memory boosting signal.
The team also tested the consequence of disrupting 50 per cent of GPR158 function in young mice. Doing so led to a 70 per cent decrease in the amount of RbAp48 protein produced by the RbAp48 gene, similar to what would happen naturally in aged brains.
鈥淚t鈥檚 the first time we show the detailed pathway between RbAp48 and osteocalcin,鈥� Kandel says. 鈥淚n the future, it [may be] possible to develop a form of GPR158 that can be administered to help reverse age-related memory loss.鈥�
Cell
