The neurons that make up your enteric nervous system 鈥� the 鈥渂rain鈥� in your gut 鈥� are almost entirely replaced every two weeks, a study in mice suggests. What鈥檚 more, an imbalance in the gut鈥檚 ability to repopulate itself with new neurons and clear out the dead ones could lead to Parkinson鈥檚 disease.
鈥淚t鈥檚 problems with the balance of the turnover of cells, not the neurons themselves, that can cause gastrointestinal problems and diseases,鈥� says Subhash Kulkarni聽at Johns Hopkins University, Maryland, who presented his findings this week at the .
He and his team found that intestinal neurons in the gut lining of mice are constantly dying at a fairly high rate. Nearly a third of mice鈥檚 gut neurons were lost after seven days. But the dead neurons don鈥檛 build up, so something must be clearing out the debris.
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In both the large and small intestine, the team found neurons being engulfed by macrophages 鈥� a kind of immune cell that eats bacteria and viruses.
Cellular turnover
Kulkarni and his team realised that the gut must produce new cells to replace the neurons that have died and been swept away. They discovered that the gut has stem cells that proliferate extremely quickly. In the mice, they saw that after two weeks, 88 per cent of the neurons situated between the two layers of muscles in the small intestine were newly formed. In other words, there鈥檚 a large amount of cellular turnover 鈥� but the number of neurons remains the same, Kulkarni says.
Recent studies have found that the buildup of a protein called alpha synuclein in the gut may stifle nerve signals in the brains of people with Parkinson鈥檚, a degenerative disease marked by tremors and stiffness. Kulkarni suspects the聽alpha synuclein build up might be a consequence of neuron turnover.
鈥淚f something goes wrong with the cleanup mechanisms, or we get crosstalk between the constant generation of new neurons and the constant cleanup, then you鈥檙e going to have an accumulation of debris,鈥� he says. 鈥淎nd the more debris that accumulates, the larger the alpha synuclein clumps can get.鈥�
Kulkarni聽says his team has preliminary data from a new study that supports the idea.聽By聽altering either how many macrophages are present or how quickly neurons repopulate in the mouse gut, the researchers knock the see-saw of cell birth and death out of whack. When they do so, they see the beginnings of buildup of the proteins that lead to Parkinson鈥檚, says Kulkarni.
鈥淚 don鈥檛 doubt their findings, but I don鈥檛 think it鈥檚 the whole story,鈥� says Ruth G. Perez, a Parkinson鈥檚 researcher at Texas Tech University in El Paso. 鈥淚f the neuronal turnover is so rapid, why do we still see this buildup of proteins in Parkinson鈥檚 patients?鈥�
She says the neurons may not all last for the same amount of time, and that they may die off and be replenished in overlapping waves.
