Researchers at the School of Medicine at The University of Texas Health Science Center at San Antonio were able to enhance learning and memory in young mice, while improving these faculties in old mice by adding rapamycin to the mice’s diet.
Rapamycin, a bacterial product first isolated from soil on Easter Island, is an antifungal agent administered to transplant patients to prevent organ rejection. The drug is named for Rapa Nui, the Polynesian name for Easter Island, famed site of nearly 900 mysterious monolithic statues.
The drug helped the young mice learn — and remember what they learned — while the older mice fed rapamycin “actually showed an improvement, negating the normal decline that you see in these functions with age,” said Veronica Galvan, Ph.D., assistant professor of physiology at the Barshop Institute for Longevity and Aging Studies, part of the UT Health Science Center.
The drug also lowered anxiety and depressive-like behavior in the mice, factors that impair cognitive performance in humans, according to Galvan.
Lead author Jonathan Halloran conducted tests to measure these cognitive components in the rodents. While mice are burrowers that prefer tunnels with walls, Halloran used an elevated maze of tunnels that led to a catwalk to help him observe the mice better.
As the rodents approached the catwalk, Halloran noted, “all of a sudden the mice are in open space.”
“It’s pretty far from the floor for their size, sort of like if a person is hiking and suddenly the trail gets steep.”
Mice with less anxiety were more curious to explore the catwalk. “We observed that the mice fed with a diet containing rapamycin spent significantly more time out in the open arms of the catwalk than the animals fed with a regular diet,” Halloran said.
The second test measured depressive-like behavior in the rodents. Mice do not like to be held by their tails, which is the way they are moved from cage to cage. Inevitably they struggle to find a way out. “We can measure how much and how often they struggle as a measure of the motivation they have to get out of an uncomfortable situation,” Galvan said.
Some mice barely struggle to get free, but if an antidepressant is administered, they struggle a lot more, she said. This behavior is very sensitive to the action of antidepressants and is a reliable measure of whether a drug is acting like an antidepressant, she added.
“We found rapamycin acts like an antidepressant — it increases the time the mice are trying to get out of the situation,” she said. “They don’t give up; they struggle more.”
The reductions of anxiety and depressive-like behavior in rapamycin-treated mice held true for all ages tested, from 4 months (college age in human years) to 12 months old (the equivalent of middle age) to 25 months old (advanced age).
The researchers measured levels of three neurotransmitters: serotonin, dopamine and norepinephrine. All were significantly augmented in the brains of mice treated with rapamycin, said Galvan, who said this is “something we are going to pursue in the lab.”
The study, funded by the National Institutes of Health, the Alzheimer’s Association and the Ellison Medical Foundation, was published in the journal Neuroscience.