Adult mouse gut makes new neurons

Study also finds nerve cell growth can be stimulated in the mice

A new way to treat digestive disorders may be hidden in the bowels of mice. Researchers report in the Aug. 5 Journal of Neuroscience that new gut nerve cells are born in adult mice and that the process can be sped up. The find suggests that gastrointestinal disorders may one day be treated with drugs that could stimulate the generation of nerve cells.

NERVES IN THE GUT Newly generated neurons (red) born in an adult mouse’s colon sit near older nerve tissue (green). Liu et al./Journal of Neuroscience

For a long time scientists thought people were born with all the neurons they would ever have. Recently researchers have found a couple of exceptions in the brain: Neurons for smelling and remembering are produced in the brain continuing into adulthood (SN: 9/27/08)

Although scientists had found that the guts of adult mice contain stem cells with the potential to become neurons, evidence for regeneration had only been found in cells in petri dishes and in very young mice. Baby neurons, if they did form in mature mice, apparently grew too rarely and too slowly to be detected.

“We knew new neurons had to develop in the gut,” based on the evidence, says developmental biologist Allan Goldstein of Massachusetts General Hospital in Boston, who was not involved in the study. “But to demonstrate how that process occurs and how it can be stimulated in vivo is novel and exciting.”

Michael Gershon of Columbia University and his colleagues tried to boost their chances of seeing the elusive new neurons. The team flooded the guts of adult mice for a full week with a molecular marker that labeled all the newborn cells in the mice’s guts. Over time, these markers were diluted in non-neuron gut cells, which continue to reproduce. But because neurons do not regenerate themselves, any new neurons born during that week retained the marker.

After waiting up to six months, the team found what it was looking for: a small number of cells had retained the marker, suggesting that new neurons were being created in the stomach and intestines of the adult mice.

In another part of the study, the team found a way to stimulate the birth of new neurons. Research has shown that drugs that target a serotonin receptor called 5-HT4 can alleviate neurointestinal disorders such as chronic constipation and irritable bowel syndrome. Gershon’s team found that two molecules known to interact with the receptor seemed to speed the process of neurogenesis and maintain existing neurons, opening the possibility of developing new drugs that can prevent damage to nerve cells in the gut and produce new nerve cells. Furthermore, when the researchers disabled the 5-HT4 in mice, the mice grew fewer new gut neurons in early adulthood and entered old age with fewer total gut neurons (and more intestinal difficulties) than the normal mice.

“It’s really interesting from a developmental perspective,” comments neurobiologist Jack Mosher of the University of Michigan in Ann Arbor. But, he says, it’s too early to tell whether there are any therapeutic implications.

Goldstein says the next step is to try to understand whether same process would work in adult humans. Though that is not yet clear, he says, “the promise is definitely there based on these results.”

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