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Neurons in the gut are replaced every two weeks BY CHELSEA WHYTE The neurons that make up the “brain” in your gut are almost entirely replaced every two weeks, a study in mice suggests. What’s more, an imbalance in the gut’s ability to repopulate itself with new neurons and clear out the dead ones could lead to Parkinson’s disease. Subhash Kulkarni at Johns Hopkins University in Maryland and his colleagues found that neurons in the gut lining of mice are constantly dying at a high rate. These cells are part of the enteric nervous system, the body’s “second brain”. 1 A mouse loses nearly a third of its gut neurons every seven days. But the dead neurons don’t build up, so something must be clearing out the debris. In both the large and small intestine, Kulkarni’s team found neurons being engulfed by macrophages, a kind of immune cell that eats bacteria and viruses. Kulkarni and his team realised that the gut must produce new cells to replace the neurons that have died and been removed. They discovered that the gut has stem cells that proliferate extremely quickly. After two weeks, 88 percent of the neurons situated between the two layers of muscles in the mouse small intestine were newly formed. In other words, there is a large amount of cellular turnover, but the number of neurons remains the same, says Kulkarni. He presented the study this week at the Society for Neuroscience annual meeting in San Diego. Recent studies have found that the build-up of a protein called alpha-synuclein in the gut may stifle nerve signals in the brains of people with Parkinson’s, a degenerative disease marked by tremors and stiffness. Kulkarni suspects that alpha-synuclein build-up is a consequence of neuron turnover. “If something goes wrong with the clean-up mechanisms, or we get crosstalk between the constant generation of new neurons and the constant clean-up, then you’re going to have an accumulation of debris,” he says. “And the more debris that accumulated, the larger the alpha- synuclein clumps can get.” Kulkarni says his team has preliminary data that supports the idea. By altering either howmany macrophages are present or how quickly neurons repopulate in the mouse gut, the researchers knock on the see-saw of cell birth and death out of whack. When they do so, they see the beginnings of the build-up of the proteins that lead to Parkinson’s, says Kulkarni. Ruth Perez, who studies Parkinson’s at Texas Tech University, welcomes the new findings. But she thinks more work needs to be done before their significance is clear. 1 Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis. Kulkarni S, Micci MA, Leser J, Shin C, Tang SC, Fu YY, Liu L, Li Q, Saha M, Li C, Enikolopov G, Becker L, Rakhilin N, Anderson M, Shen X, Dong X, Butte MJ, Song H, Southard-Smith EM, Kapur RP, et al (2017) Proc Natl Acad Sci U S A 114:E3709 –E3718. © 2018 New Scientist Ltd. All rights reserved. Distributed by Tribune Content Agency, LLC 10 Headlines