A new US study has added to existing knowledge about the million or so brain cells in our gut by using lab mice to show that it can also grow new ones under the control of the neurotransmitter serotonin. The findings could be used to develop new drugs for gastrointestinal disorders, which affect around 25 per cent of adults in the US every day, and come second only to the common cold as the reason most Americans miss work, said the researchers.
The study, which is the first to show that the adult intestine can make new neurons in the enteric nervous system (ENS), was led by Drs Mintsai Liu, and Michael D Gershon, at Columbia University in the City of New York and is published in the 5 August issue of The Journal of Neuroscience.
Liu and Gershon and colleagues used a serotonin-related drug to add neurons to the adult enteric nervous system, which they said was the first time this had been done.
“Conceivably, treatment with compounds of this type can be used in the future to help repair a damaged or congenitally defective enteric nervous system without resorting to an invasive procedure,” they told the media.
So what is the ENS?
Scientists have found evidence of what many of us already suspected: our brains and our guts “talk” to each other. In fact they are so intimately connected that some believe the gut and the brain should be viewed as part of one system.
We all know our gut is sensitive to emotions: we have “butterflies” in our stomach, we feel nauseous in certain situations, and some experiences can be “gut wrenching”. These are all visceral manifestations of anxiety, anger, sadness, elation. Doctors know it is important to bear this in mind when treating gastrointestinal disorders that appear to have no obvious physical or infectious cause.
Our 30-foot long gut is embedded with cells of the enteric nervous system, the ENS, a complex system of around 100 million nerves which is often referred to as our “second brain”. The ENS supervises the processes of digestion and stays in close contact with, and is heavily influenced by, the central nervous system (the CNS) which comprises the brain and spinal cord.
When the fetus grows in the womb, the ENS develops from the same tissue as the CNS, and in many respects its structure mirrors that of the brain in that it has sensory and motor neurons supported by a protective structure of glial cells which acts a bit like “scaffolding”. The ENS and CNS also use many of the same chemical messengers or neurotransmitters inclusing acetylcholine and serotonin. Such communication explains obvious things like why we stop eating when we are full, or why we feel sick or lose our appetite on the morning of an important exam.
Until recently, neuroscientists believed that new neurons only grew in fetal brains and the neurons we had at birth were the ones we kept for life and that was it. But now we know that the CNS does make new neurons throughout adulthood.
And with this study, Liu and Gershon and colleagues show that under certain conditions, such as those controlled by serotonin, the ENS can also make new neurons.
It was about 4 decades ago that researchers discovered that our bowels contain high levels of serotonin 5-HT. In fact a recently developed drug, tegaserod, designed to treat constipation and irritable bowel syndrome targets the serotonin receptor 5-HT4. However, the drug, which received approval from the US Food and Drug Administration in 2002, was later withdrawn because it was thought it might cause heart attacks.
Liu and Gershon and colleagues found that the 5-HT4 receptor and, by inference, serotonin, are intimately involved in controlling the production of new ENS neurons after birth.
They compared mice that had the 5-HT4 receptor (“normal” mice) with mice that did not. Compared with the normal mice, the mice that lacked the receptor had the same number of neurons at birth, but they waned as the mice got older.
Also, when the researchers gave the normal mice a drug that stimulated the 5-HT4 receptor, they found not only that it enhanced the post-birth production of ENS neurons but it protected the ones that were already there.
Dr Arturo Alvarez-Buylla of the University of California, San Francisco, an expert in stem-cell neurobiology and developmental neuroscience who was not involved with the study, said that Liu and Gershon and colleagues had helped to clarify some unanswered questions about the gastrointestinal system. He said their finding:
“Not only suggests that new enteric neurons can be generated in the adult, but that activation of the serotonin receptor is required for this process.”
“The enteric nervous system has a very large number of neurons, yet we know very little about their progressive loss during life and whether they can be regenerated,” he added.
The research was funded by the National Institutes of Health and Novartis, the drug company that makes tegaserod.
Source: Society for Neuroscience; The Sensitive Gut, Harvard Health Publications.
Written by: Catharine Paddock, PhD