Researchers at the University of California, Los Angeles have identified a neurological mechanism behind memory linking.
Researchers at the University of California, Los Angeles have identified a neurological mechanism behind memory linking. Manipulation of this mechanism has been shown to restore memory in mouse models, and researchers were stunned to learn that the U.S. Food and Drug Administration (FDA) has already approved a drug that works the same way. The findings were published earlier this week in Nature.
The established understanding of memory linking is described in the published article as follows: “events that are experienced close in time are more likely to be meaningfully associated, whereas those that are experienced with a longer interval are not. How the brain segregates events that are temporally distinct is unclear.”
To uncover the brain’s memory linking pathway, the research team took a closer look at the C-C chemokine receptor type 5 (CCR5) gene. This gene has gained notoriety in the past as the gene that is associated with AIDS patients’ memory loss because it may determine which memories are significant enough to establish memory linkage. The CCR5 gene receptor has a role in the mediation of immune and inflammatory responses. The FDA approved maraviroc, a CCR5 receptor antagonist, in 2007 as a treatment that stops the R5 virus from entering a patient’s white blood cells.
Professor of Neurobiology and Psychiatry at UCLA’s David Geffen School of Medicine, Alcino Silva, had previously studied maraviroc in mouse models albeit for a different purpose. In those laboratory studies, older mice that previously were unable to link memories had their abilities restored after being given maraviroc. This was done by suppressing CCR5 activity in the subjects’ brains.
In Silva’s recent laboratory experiments, increased expression of CCR5 was seen in mouse neurons. Further, CCL5, a ligand of CCR5, impaired the memory of the subjects at higher expression levels. The focus turned to whether manipulation of the gene and its ligand could affect memory.
The researchers tested the theory by evaluating whether mice could link memories of two separate cages. To do this, the lab deleted the CCR5 gene in the subjects’ brains altogether, using gene knockout techniques. After the deletion, the mice were able to link memories that unaltered mice were not- the same effect seen in mice that had been given maraviroc. Alternatively, increasing CCR5 activity during the test caused the mice to forget the link between the two cages.
Silva explained how the team will approach testing maraviroc as a memory loss preventative.
“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,” he said. “Once we fully understand how memory declines, we possess the potential to slow down the process.”
Memory loss is a clinical manifestation of dozens of afflictions, ranging from dementia to alcoholism or even a traumatic brain injury. This symptom can be the reason a patient needs to enter supportive care, stripping freedom from daily life. While maraviroc may not be suitable for treating memory loss for all patients, this discovery could be beneficial in helping restore the memories of those whose memory loss is associated with CCR5.
