HIV Drug Helps Memories Stay Connected With Age, Intriguing Mouse Study Finds

 

Our brains seldom keep single memories; instead, they aggregate them together such that recalling one key experience prompts the recall of others that are linked in time. However, as we become older, our brains lose the ability to connect memories together.

UCLA scientists have now found a critical chemical process that underpins memory linkage. They've also discovered a means to restore this brain function in middle-aged rats, as well as an FDA-approved medicine to do it.

The findings, which were published in Nature, reveal a novel strategy for improving human memory in middle age and a possible early intervention for dementia.

"Our memories are a huge part of who we are," Alcino Silva, a distinguished professor of neuroscience and psychiatry at UCLA's David Geffen School of Medicine, noted. "The ability to link related experiences teaches how to stay safe and operate successfully in the world."

A bit of Biology 101: cells are densely packed with receptors. A chemical must latch onto its corresponding receptor to get entry to a cell, which works like a doorknob.

The UCLA researchers focused on a gene called CCR5, which codes for the CCR5 receptor, which HIV uses to infect brain cells and cause memory loss in AIDS patients.

CCR5 expression was shown to impair memory recall in Silva's lab's previous research.

Silva and his colleagues uncovered a crucial mechanism behind mice's capacity to connect memories from two distinct cages in the current investigation. The scientists were able to witness neurons activating and establishing new memories thanks to a small microscope that provided a window into the animals' brains.

Memory linking was disrupted when CCR5 gene expression was increased in the brains of middle-aged mice. The animals had forgotten that the two cages were connected.

When the CCR5 gene was removed from the mice, they were able to associate memories that normal mice couldn't.

Silva has previously researched maraviroc, a medicine that was licensed by the US Food and Drug Administration in 2007 for the treatment of HIV infection. Maraviroc also inhibited CCR5 in the brains of mice, according to his research. "When we gave maraviroc to older mice, the drug duplicated the effect of genetically deleting CCR5 from their DNA," Silva, a UCLA Brain Research Institute member, explained. "The older animals were able to link memories again."  

Maraviroc might be used off-label to assist recover middle-aged memory loss and correct HIV-related cognitive deficiencies, according to the findings.

"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," Silva added. "Once we fully understand how memory declines, we possess the potential to slow down the process."

Which begs the question: why does the brain require a gene that prevents memories from being linked?

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

The study was financed by the National Institute on Aging. Yang Shen, a UCLA postdoctoral researcher, and Miou Zhou, a Western University assistant professor, collaborated on the work.