By using a tiny microscope to study the brain activity of rodents, scientists at the University of California, Los Angeles (UCLA) have uncovered a key mechanism behind the retention of memories, and shown how targeting it could strengthen human memory during middle age. Their approach involves an existing drug used to treat HIV, and the researchers believe repurposing it could serve as an early intervention for conditions like dementia.
The study focuses on the way memories are formed in the human brain, which stores them as sets of related experiences rather than one-off recollections. This is why remembering one particular incident might lead us to think of others that occurred at a similar time or place, but this type of "memory linking" ability is known to deteriorate with age.
“Our memories are a huge part of who we are,” said Alcino Silva, an author of the research. “The ability to link related experiences teaches us how to stay safe and operate successfully in the world.”
To better understand the molecular machinery behind memory linking, the scientists leveraged a cutting-edge research tool described as a miniscope. This device can be mounted on the heads of animals to observe neurons firing and memories being formed, enabling scientists to study the different ways cells work as the brain senses, learns and executes actions.
This miniscope was used to study mice, with the scientists focusing their attention on a type of molecule called CCR5. Previous research from the group had shown that the amount of this molecule expressed in the brain rises as we age, and this increase leads to a reduction in memory recall.
In their experiments on genetically engineered mice, the team was able to show that boosting the gene that encodes for CCR5 impacted on their memory, making them unable to link memories of experiences in different cages. Deleting the CCR5 gene restored their memory, and enabled them to link these memories, where normal mice could not.
The receptors that CCR5 molecules use to gain entry into the brain are the same receptors that HIV uses to infect brain cells and drive the memory loss seen in AIDS patients. In 2007, the US Food and Drug Administration approved a drug called maraviroc to treat HIV infection, which works by binding to these receptors to block the virus' entry into cells. In giving the drug to older mice, the team found it had the same effects on memory as their careful genetic tinkering.
“When we gave maraviroc to older mice, the drug duplicated the effect of genetically deleting CCR5 from their DNA,” said Silva. “The older animals were able to link memories again.”
According to the scientists, the results suggest that in addition to treating cognitive decline in AIDS patients, maraviroc could be used more broadly as a way of restoring or preventing age-related memory loss associated with dementia.
“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,” said Silva. “Once we fully understand how memory declines, we’ll possess the potential to slow down the process.”
The research was published in the journal Nature.