Wyoming researcher studies ‘second brain’ in gut tissues

When we eat a meal, we’re generally confident that our bodies will process the fuel efficiently and naturally. After all, it’s been happening continuously since the day we were born. But what is it really that we are placing our faith in?

Dr. Paul Wade

Our gastrointestinal systems perform their functions without us having to consciously think about it. Conversely, consider how we can use our central nervous system (CNS) to control the rate of our breathing. We can stop our breathing. This is because the neurons of the CNS are located in the brain and the spinal cord.

The neurons that control functions in our bowels, however, are located entirely within the gut. Sometimes called the “little brain in the gut,” this system — the enteric nervous system (ENS) — does the thinking for us when it comes to making sure water is absorbed from fecal matter and that the colon constricts and retracts to move waste down.

“The components of the ENS are entirely in the gut. Because of this, the bowel can be disconnected from the brain and spinal cord and studied as it carries out reflex behaviors,” explains Dr. Paul Wade, an assistant professor of zoology and physiology and of human medicine at the University of Wyoming.

Specifically, Wade studies the actions in the ENS of several substances that neurons use to communicate with one another, such as the neurotransmitter serotonin. His research suggests that serotonin plays an important role regulating motility in the colon; essentially, it appears serotonin ensures that neurons up and down the colon are communicating so that a coordinated constriction and relaxation occurs to move waste down. By altering serotonin levels in colon specimens in the lab, Wade and colleagues have recorded changes in the rate of motility.

Wade, the 15th annual Science in Medicine WWAMI lecturer, will give a detailed talk on his research, titled “Serotonin in the Second Brain: Functions of Serotonin in the Enteric Nervous System,” on Wednesday, Oct. 20, from noon to 1 p.m. in room T-625 of the Health Sciences Center.

Evidence that further suggests serotonin is important in regulating the rate of motility in the colon is that patients who take Prozac — a drug that increases serotonin levels in the CNS — frequently experience gastrointestinal dysfunctions, such as diarrhea or constipation.

“A drug that increases serotonin in the central nervous system is going to affect the bowel because serotonin is a major player in the gut ENS,” Wade said.

One aspect of Wade’s research is understanding the changes that occur in the ENS as we age. Approximately one-half of the seniors admitted to nursing homes in the nation suffer from fecal incontinence, diarrhea and constipation.

Wade and his colleagues conduct studies in which they apply antibodies that attach to specific neurons in the ENS of the colon. By attaching a fluorescent molecule to the antibodies, they can then identify and analyze the cells with a fluorescent microscope. In studies of young and older colon segments from rodents, the researchers have found there is a decrease in the number of certain colonic neurons that control smooth muscle cells in the bowel. Their research also suggests that some of the lost motility in the colons of aged animals can be restored by adding serotonin.

Another method, in addition to fluorescent microscopy, Wade employs in the lab is to study specimens in an “organ bath” — a chamber that replicates the natural liquid state of the body in which researchers place isolated pieces of the intestine.

By placing an artificial pellet in an animal intestine, researchers study exactly how the pellet moves down the intestine by reflex actions mediated by the ENS. They then record the normal rate of motility. By adding drugs and monitoring the rate of motility and the reactions of neurons in the wall of the colon, they are able to determine the effects of drugs and the functions of the neurons.

The fact that the ENS is autonomous of the brain and spine is not to say that the two do not affect each other, Wade added. Anyone who has felt butterflies, or stage fright so severe that they have needed to find a fast path to the restroom, inherently understands this connection. Yet the mechanisms that controls this connection are poorly understood.

“It used to be thought that this is a simple system to study, but there are as many neurons in the gut as there are in the spinal cord,” Wade said.

In 1997, Wade moved from the Columbia University College of Physicians and Surgeons in New York City to become the founding instructor in human anatomy and embryology for the University of Wyoming’s WWAMI Program.

WWAMI is the regional medical education program of the UW School of Medicine. It is named for the participating states of Washington, Wyoming, Alaska, Montana and Idaho.

At Columbia, Wade studied with Michael D. Gershon, who proved that serotonin is a neurotransmitter in the ENS and who recently published a popular book on the subject, titled “The Second Brain.” Accustomed to classes of 150 students, Wade said he accepted the position in Wyoming to teach in a more individualized, participatory manner and as an opportunity to help launch a new endeavor in medical education.

Wade received a B.S. in zoology from the University of Nebraska in Lincoln in 1975, M.S. in anatomy and physiology from Kansas State University in Manhattan in 1978 and a Ph.D. in biochemistry from the University of Nevada in Reno in 1987. ¶

Will Morton