The human brain usually stores memories in groups so that the recollection of one significant memory triggers the recall of others connected by time. With ageing, the brain gradually loses this ability to link related memories.
Now, researchers have discovered a key molecular mechanism behind this memory linking, and also identified a way to restore this brain function in middle-aged mice. They also found an anti-HIV drug that can do this.
Published in Nature, the findings suggest a new method for strengthening human memory in middle age and a possible early intervention for dementia.
“Our memories are a huge part of who we are,” explained Professor Alcino Silva. “The ability to link related experiences teaches how to stay safe and operate successfully in the world.”
The team from UCLA focused on a gene called CCR5 that encodes the CCR5 receptor – the same one that HIV hitches a ride on to infect brain cells, resulting in memory loss in AIDS patients.
In previous work, Prof Silva’s lab showed that CCR5 expression reduced memory recall.
In the current study, Prof Silva and his colleagues discovered a central mechanism underlying mice’s ability to link their memories of two different cages. Using a tiny microscope, the researchers observed neurons firing and creating new memories in the brains of the mice.
They found that boosting CCR5 gene expression in the brains of middle-aged mice interfered with memory linking, with animals forgetting the connection between the two cages.
Mice with the CCR5 gene knocked out were able to link memories that normal mice could not.
Proof Silva had previously studied the anti-HIV drug maraviroc, which inhibits the entry of HIV into human cells. His lab discovered that maraviroc also suppressed CCR5 in the brains of mice.
“When we gave maraviroc to older mice, the drug duplicated the effect of genetically deleting CCR5 from their DNA,” said Prof Silva. “The older animals were able to link memories again.”
The finding suggests that maraviroc could be used off-label to help restore middle-aged memory loss, as well as reverse the cognitive deficits caused by HIV infection.
“Our next step will be to organise a clinical trial to test maraviroc’s influence on early memory loss with the goal of early intervention,” said Prof Silva. “Once we fully understand how memory declines, we possess the potential to slow down the process.”
All of this raises a question: what’s the purpose of a gene that interferes with the brain’s ability to link memories?
“Life would be impossible if we remembered everything,” said Prof Silva. “We suspect that CCR5 enables the brain to connect meaningful experiences by filtering out less significant details.”
Source: University of California – Los Angeles Health Sciences
