Intriguing mouse research finds that an HIV drug helps memories stay connected as people age.

Intriguing mouse research finds that an HIV drug helps memories stay connected as people age.

In elderly mice, a popular HIV treatment has been found to strengthen memory links. The findings may provide light on how contextual experiences are remembered in the human brain, as well as why this gets more difficult as we get older.

The HIV medicine maraviroc works by targeting a cellular protein called CCR5, which is found on the surface of white blood cells. When the HIV virus binds to one of these receptors, it can enter and multiply in the cell. However, if maraviroc arrives before, it will block the entry.

That's not all it does, though. In 2019, researchers using animal models discovered that maraviroc can aid neurons in forming new connections after a stroke.

Another mouse study has shed more information on the drug's workings, especially its impact on memory-related cells. Researchers discovered that as mice grew older, the expression of CCR5 in their hippocampal neurons rose as well.

The hippocampus is the brain's memory centre, but when CCR5 expression rises, neurons find it more difficult to link one memory to another based on context.

When researchers compared mice that expressed CCR5 to animals that did not, they discovered that the latter group was better at linking memories separated by longer periods of time.

In this situation, the recollections were centred on terror. The mice were removed from their previous environment and placed in a new one (A). They were afterwards transferred to a different situation (B). They were given a shock in context B two days later. After another two days, the animals were returned to context A to test if they were ready for the shock.

Importantly, some mice were exposed to contexts A and B within five hours of each other in the study. Others were exposed to both environments over the course of one, two, or seven days.

The authors detected high rates of freezing in context A among ordinary mice, which is a symptom of dread. However, mice with high CCR5 expression had a decreased freezing rate overall.

When the introductions were separated by two or more days, none of the mice were able to link context A to context B as efficiently. The animals were only able to do so when CCR5 was knocked out in some mice.

CCR5 has described a temporal window that exists to ensure that not all memories in the brain are linked. To preserve efficiency, some must be separated, which is most likely CCR5's involvement in contextual learning: it helps us forget unnecessary knowledge.

However, when a mammal grows older, CCR5 loses control, and even closely related circumstances are no longer remembered in the same way.

With the medication maraviroc, the failure to connect context A with context B was reversed in older mice. The results were identical to those seen in mice with CCR5 knocked out totally.

The authors write, "Unlike control mice, maraviroc-treated mice displayed memory linkage."

"In middle-aged mice, inhibiting CCR5 with maraviroc improves memory linking impairments. Overall, these findings show that CCR5 expression is involved in both decreasing the temporal window for memory linking and age-related memory losses."

If these findings hold true in humans, CCR5 could be a promising pharmacological target for people who have trouble organising memories.

The researchers are already planning a clinical experiment to see how maraviroc affects early memory loss in humans.

"Once we fully understand how memory deteriorates, we'll be able to slow it down," says Alcino Silva, a neurobiologist and psychiatrist at the University of California, Los Angeles.