杏吧原创

Parkinson鈥檚 disease may start in the gut and travel to the brain 鈥� but it can also spread from the brain to the gut, according to findings in baboons.

Misfolded proteins thought to trigger brain damage seem to travel in the blood, and cause equal amounts of brain cell death whether they originate in the brain or the gut.

People with Parkinson鈥檚 disease often experience gastrointestinal symptoms, such as constipation. Research conducted over the past 17 years or so suggests that the misfolded proteins that characterise the disease might spread from the gut to the brain,聽but much of this work has been conducted in mice.

To get a better idea of what might be happening in humans, Benjamin Dehay at the University of Bordeaux in France and his colleagues studied 15 baboons of various ages, ranging from the human equivalents of teenagers to middle-aged adults. They took misfolded alpha-synuclein, which is thought to trigger brain damage in people with Parkinson鈥檚, from donated brains of people who had died with the disease, and then implanted it into either the guts or the brains of two-thirds of the baboons.

Two years later, the researchers looked at the baboons and found the misfolded protein in both the brains and guts of all the baboons given it, regardless of where it had originally been implanted. All these animals also showed signs of brain damage and had lost around 40 per cent of dopamine-producing cells in a region of the brain that is important for movement. The extent of the damage 鈥渨as really unexpected鈥�, says Dehay.

The baboons hadn鈥檛 yet developed any problems with movement, but that is because these symptoms aren鈥檛 thought to appear in humans until people lose around half of these brain cells, says Dehay. The researchers don鈥檛 know whether the baboons had any gastrointestinal symptoms. They were part of a large group living together and the animals generally behave quite aggressively, so it was difficult to assess their faeces or any changes in behaviour, says Dehay.

In the past, researchers have suggested that the gut-brain link in Parkinson鈥檚 disease may be connected to聽the vagus nerve, which runs all the way from the brain to the abdomen. But Dehay and his team couldn鈥檛 find the misfolded protein in this nerve. Instead, they found it in the baboons鈥� blood, suggesting it may travel around the body via the bloodstream.

Denise Barbut, a neuroscientist exploring treatment for Parkinson鈥檚 disease at biotechnology firm Enterin, isn鈥檛 so sure. Previous research in rodents has shown that alpha-synuclein can travel along the vagus nerve in a matter of days. The protein may have already travelled between the brain and the gut along this route and left the vagus nerve by the time the researchers looked two years later, she says.

Yet Barbut does believe there is enough evidence to suggest this two-way spread of misfolded proteins between brain and gut is likely to be happening in humans. Barbut is investigating a potential treatment for Parkinson鈥檚 disease that targets the gut rather than the brain.

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