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How does the brain connect meaningful memories?

Instead of recording single memories, our brains store them into groups so that the recollection of a significant memory triggers the recall of other connected ones. However, as we age, our brains gradually lose the capacity to link related memories. 

A team of researchers led by the University of California, Los Angeles (UCLA) has now discovered a key molecular mechanism behind memory linking, together with a way of restoring this crucial brain function in middle-aged mice. These findings could offer new methods for strengthening human memory in middle age and developing early interventions against dementia and other neurodegenerative diseases.

“Our memories are a huge part of who we are,” explained study senior author Alcino Silva, a distinguished professor of Neurobiology and Psychiatry at UCLA. “The ability to link related experiences teaches how to stay safe and operate successfully in the world.”

Professor Silva and his team focused on a gene called CCR5 which encodes a receptor that the HIV virus uses to infect brain cells and cause memory loss in AIDS patients. By performing several experiments on laboratory mice, the scientists found that boosting CCR5 expression in the brains of middle-aged mice interfered with memory linking. However, when deleting this gene, the mice were able to link memories that normal mice could not.

“Life would be impossible if we remembered everything,” said Professor Silva. “We suspect that CCR5 enables the brain to connect meaningful experiences by filtering out less significant details.”

The researchers also found that maraviroc – a drug used against HIV infections since 2007 – also suppressed CCR5 in mice’s brains. “When we gave maraviroc to older mice, the drug duplicated the effect of genetically deleting CCR5 from their DNA. The older animals were able to link memories again,” reported Professor Silva. Thus, maraviroc could be used off-label to restore middle-age memory loss, in addition to reversing the cognitive deficits induced by HIV infections.

“Our next step will be to organize a clinical trial to test maraviroc’s influence on early memory loss with the goal of early intervention. Once we fully understand how memory declines, we possess the potential to slow down the process,” concluded Professor Silva. 

The study is published in the journal Nature.

By Andrei Ionescu, Staff Writer

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