The neurons that make up your enteric nervous system – 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.
“It’s problems with the balance of the turnover of cells, not the neurons themselves, that can cause gastrointestinal problems and diseases,” says Subhash Kulkarni 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’s gut neurons were lost after seven days. But the dead neurons don’t 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 – 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’s a large amount of cellular turnover – 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’s, a degenerative disease marked by tremors and stiffness. Kulkarni suspects the alpha synuclein build up might be a consequence of neuron turnover.
“If something goes wrong with the cleanup mechanisms, or we get crosstalk between the constant generation of new neurons and the constant cleanup, then you’re going to have an accumulation of debris,” he says. “And the more debris that accumulates, the larger the alpha synuclein clumps can get.”
Kulkarni says his team has preliminary data from a new study that supports the idea. By 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’s, says Kulkarni.
“I don’t doubt their findings, but I don’t think it’s the whole story,” says Ruth G. Perez, a Parkinson’s researcher at Texas Tech University in El Paso. “If the neuronal turnover is so rapid, why do we still see this buildup of proteins in Parkinson’s patients?”
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.
