Existing Drug Rejuvenates Brains Of Elderly Rats

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The human population is growing older, and unless we age healthily, the elderly can be a huge social and public health strain. Many scientists are therefore hunting for ways to reduce some of the problems that come with aged bodies, in particular cognitive impairments or neurodegenerative diseases, and scientists may have just stumbled upon a very promising candidate: an asthma drug.

You might be thinking that this is a pretty bizarre link, a respiratory disease and brain function, but there is method behind the madness. While cause versus effect isn’t entirely clear, a common hallmark linked with age-associated cognitive decline is inflammation of the brain, driven by defence cells called microglia. Asthma is an inflammatory disease of the airways, so scientists therefore reasoned that it might be possible to repurpose the powerful anti-inflammatory drugs used for this condition in order to slow or reverse brain aging.

Researchers from Paracelsus Medical University, Austria, decided to test this hypothesis out, and focused on a marketed drug called montelukast. This works by blocking receptors for molecules called leukotrienes which mediate inflammatory responses, and while their role in the brain is unclear, heightened levels have been observed in the aged brain.

For their investigation, published in Nature Communications, the scientists administered both young and aged rats montelukast for six weeks and compared their performance on a test of learning and memory where the rats had to remember the location of a hidden platform in a water tank. Aged animals normally have deficits in this task, taking longer than their younger counterparts to learn, but remarkably montelukast treatment was found to close the gap between the two groups, with the old rats performing just as well as young rats. No improvement on the performance of the young rats, however, was observed.

To find out what could be going on at the cellular level, the scientists examined the animals’ brains and, sure enough, discovered a reduction in neuroinflammation in those belonging to the aged animals. Not only that, but they also found that cells in the hippocampus – crucial for learning and memory – went on a growth spurt, creating new functional neurons. And when the scientists tested out the drug on brain cells in a dish, they observed the same boost in proliferation, but not in cells in which a particular leukotriene receptor, called GPR17, was deleted by the researchers.

But why are we only seeing these effects in old brains? “Good question!” lead researcher Ludwig Aigner said to IFLScience. “There are several possible reasons, but the point we want to make is that although leukotrienes are found in the young brain, they are present at much higher levels in aged brains and those of individuals with neurodegenerative diseases. So it’s possible that blocking their receptors in young brains has no effect because the leukotriene signaling mechanisms are not yet activated.”

Perhaps the most encouraging part of this study is the fact that the drug is already on the market, meaning progressing towards human trials shouldn’t take as monstrously long as with a new compound. And Aigner says the team has already applied for funding to do so, looking at the drug’s efficacy in one type of dementia. But the drug’s newfound usefulness may not end there: Aigner’s team has also gathered some very preliminary data on animal models of Parkinson’s disease which once again showed a restoration of cognitive function. “But we don’t know the underlying mechanism yet,” he says. 

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