The brain’s blood vessels (artificially coloured) are lined with slick molecules, forming a guard against inflammation in brain tissue.Credit: Vsevolod Zviryk/Science Photo Library
A slimy barrier lining the brain’s blood vessels could hold the key to shielding the organ from the harmful effects of ageing, according to a study in mice.
The study showed that this oozy barrier deteriorates with time, potentially allowing harmful molecules into brain tissue and sparking inflammatory responses. Gene therapy to restore the barrier reduced inflammation in the brain and improved learning and memory in aged mice. The work was published today in Nature1.
The finding shines a spotlight on a cast of poorly understood molecules called mucins that coat the interior of blood vessels throughout the body and give mucus its slippery texture, says Carolyn Bertozzi, a Nobel-prizewinning chemist at Stanford University in California and a lead author of the study. “Mucins play a lot of interesting roles in the body,” she says. “But until recently, we didn’t have the tools to study them. They were invisible.”
Snotty barrier
Mucins are large proteins decorated with carbohydrates that form linkages with one another, creating a water-laden, gel-like substance. They are crucial constituents of the blood–brain barrier, a system that restricts the movement of some molecules from the blood into the brain.
Researchers have long sought ways to sneak medicines past this barrier to treat diseases of the brain. Previous work also showed that the integrity of the barrier erodes with age2, suggesting that it could be an important target for therapies to combat diseases associated with ageing, such as Alzheimer’s disease.
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But scientists knew little about the contribution of mucins to these changes, until Sophia Shi, a graduate student at Stanford, decided to focus on a mucin-rich layer called the glycocalyx, which lines blood vessels. Shi and her colleagues looked at what happens to the glycocalyx in the brain as mice age. “The mucins on the young blood vessels were thick and juicy and plump,” says Bertozzi. “In the old mice, they were thin and lame and patchy.”
The team went on to find that mucins in a particular class were less abundant in old mice than in young mice. The scientists also showed that a decrease in the activity of enzymes needed to produce these mucins caused the blood–brain barrier to become leakier.
And bolstering the activity of those enzymes in old mice reduced the leakage and improved the animals’ performance on learning and memory tests. Old mice can be forgetful, says Bertozzi. “They can’t get out of the maze like they used to. But they do better on those tests after we restore the mucin barrier.”
