Rapamycin, a bacterial product first discovered in a soil sample from Easter Island – also known as Rapa Nui, hence the name – is an immunosuppressant drug used to prevent rejection in organ transplants that has now been found to enhance learning and memory in young and old mice alike. Researchers at the School of Medicine at The University of Texas (UT) Health Science Center San Antonio made the discovery while looking for a way to prevent the decline in cognitive skills that comes with age.
The researchers added rapamycin, which is also known as sirolimus and is marketed by Pfizer under the trade name Rapamune, to the diet of healthy mice throughout their lifespan and found the drug's effects held true for mice of all ages.
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“We made the young ones learn, and remember what they learned, better than what is normal,” 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. “Among the older mice, the ones fed with a diet including rapamycin actually showed an improvement, negating the normal decline that you see in these functions with age.”
Dr. Galvan said the drug also lowered anxiety and depressive-like behavior in mice – both factors that impair human cognitive performance.
As burrowers that prefer tunnels with walls, mice are uncomfortable in open spaces. So, to observe the behavior of the mice, the researchers used an elevated maze that led to an open catwalk. Compared to those with a regular diet, they observed that mice fed with a diet containing rapamycin spent significantly more time exploring the catwalk, indicating they experienced less anxiety.
A second test to measure the depressive-like behavior of the rodents took advantage of the fact that mice don’t like to be held by their tails. As this is the way they are moved from cage to cage, they inevitably struggle to find a way out, and how much and how often they struggle can provide a measure of the motivation to get out of an uncomfortable situation.
Some mice barely struggle to get free, but if an antidepressant is administered they struggle a lot more. This behavior is very sensitive to the action of antidepressants and is a reliable measure of whether a drug is acting like an antidepressant, Dr. Galvan said.
“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 team says the reduction in anxiety and depressive-like behavior in the mice treated with rapamycin was observed in all ages tested, from four months of age, which equates to college age in human years, to 12 months old, which is equivalent to middle age, right through to 25 months of age, which equates to advanced age in humans.
The researchers also measured levels of serotonin, dopamine and norepinephrine, which are “happy, feel-good” neurotransmitters. All three of these chemical messengers in the brain were significantly elevated in the mice treated with rapamycin, which Dr. Galvan says may explain rapamycin’s effects.
The team’s study was published last week in the journal Neuroscience.
Source: UT Health Science Center