UCLA researchers find reducing CCR5 levels in brain may treat memory decline
By Caroline Sha
July 9, 2022 4:21 p.m.
This post was last updated August 4 at 7:43 p.m.
UCLA researchers have discovered a molecular explanation that describes how the brain links multiple memories as well as a potential treatment for memory decline.
The study, published May 25, is one of the first papers to provide a molecular explanation for how the brain connects memories of events that occurred at distinct points in time, said Alcino Silva, a distinguished professor of neurobiology, psychiatry and biobehavioral sciences, and psychology at UCLA and co-author of the study.
This connection of memories is called memory linking: after an event the brain wishes to remember has occurred, there is a window of time in which a new experience can be assigned to the same neuron, said David Clewett, an assistant professor of psychology. This means that remembering any of these connected events will activate the same neuron, he said.
The researchers discovered that when two events happen within a few hours of each other, the memories of these two events have a higher chance of being linked together, said Miou Zhou, assistant professor in the Graduate College of Biomedical Sciences at Western University of Health Sciences and co-author of the study.
A protein called CCR5, which has a role in immune responses, underlies the mechanism that regulates the length of time of this window for memory linking, Silva said, adding that the study found that CCR5 acts as a brake in the process of memory creation. When the parts of the brain responsible for memories are activated by an event, CCR5 begins to be produced in the brain, and once enough is synthesized, memories can no longer be linked to the same neuron, he said.
As people age, the ability to link memories together declines, which can lead to issues in episodic memory, which are memories of specific events in one’s life and are associative by nature, Clewett said.
The researchers found that for middle-aged mice, the mechanism of memory linking was defective but the process for individual memory creation was unchanged, Silva said. They discovered that with aging, CCR5 levels can increase and weaken the process of memory linking before one begins to have memory formation issues, he said.
Silva added that they found the drug maraviroc could reverse the changes in memory linking in middle-aged mice by decreasing the level of CCR5 in the brain.
Maraviroc is an FDA-approved drug that is currently prescribed to treat HIV, Zhou said, adding that the CCR5 is a co-receptor for HIV infection. This means that HIV uses the receptor to enter an infected person’s cells, according to ClinicalInfo.
Silva said that maraviroc could potentially fulfill the need for new memory drugs, as there are only a couple of types widely used in clinics with limited benefits for memory decline.
He added that research into maraviroc could treat memory issues associated with Alzheimer’s disease and old age, as well as other disorders.
“Memory deficits happen when we’re depressed,” Silva said. “We are experiencing higher levels of depression around the world than ever before and schizophrenia is associated with memory deficits. Cancers and treatment for cancers can be associated with memory deficits.”
One advantage of maraviroc is that it is an already FDA-approved drug and could be used in a clinical trial to test its effect on memory decline, bypassing the process of creating a new drug, Zhou said.
Zhou said the researchers believe memory linking is not completely dependent on CCR5 and that he would like to see future research look at other mechanisms involved in memory linking.
Translating experimental results in rodents to humans is another area for future research, Clewett said, adding that work needs to be done to determine how human and rodent memory compare.
Silva also said he hopes further research will be done on how the brain arranges memories and memory linking. Research in this area could affect not only clinical studies and the study of the human brain but could also impact artificial intelligence studies focused on recreating human memory processes, he added.
“We have a wide number of reasons for memory deficits, and the problem is that we have so very, very few tools to address these deficits,” Silva said. ”So we desperately need new tools, new ways of treating these memory deficits, and we really really hope that CCR5 inhibitors like the FDA-approved maraviroc will be one of those.”