Discovering How the Body Speaks Your Mind

It may be just a three-pound mass of fatty tissue, but the human brain could be the most complex living structure known. The daunting task of understanding how the brain controls all body activities and even influences our response to disease falls to neuroscientists working at the "last frontier" of biological sciences. Thousands of Gulf War veterans have returned home still suffering from the symptoms of Irritable Bowel Syndrome that began when they deployed. It was theorized that their problem was triggered by the anxiety created by war and then aggravated by living with recurrent bouts of diarrhea, constipation and abdominal pain. Now these vets are back at home, presumably having left stress behind, yet the visceral hypersensitivity and chronic abdominal pain associated with IBS persists.

OU Health Sciences Center neuroscientist Beverley Greenwood-Van Meerveld, Ph.D., is able to duplicate the veterans' mysterious and painful symptoms in her lab by injecting stress-causing corticosteroid into the amygdalas of rats. The rats don't actually develop IBS. But in lab tests they experience the same abdominal pain that afflicts the veterans and millions of other IBS sufferers. So what's going on here? Does IBS come first and anxiety follow? Or is anxiety to blame for IBS? Can anything be done to stop the pain? The answers likely lie in the complex communication system between brain and gut. Finding them requires pioneering work in neuroscience, a field described by Nobel laureate and neurobiologist Eric Kandel as the "last frontier" of biological sciences.

Since 2003, Greenwood-Van Meerveld, professor of physiology, has directed the Oklahoma Center for Neuroscience. The program was established in 1990 to provide an organization to promote and facilitate collaborations between basic and clinical researchers. The center also provides training through its own neuroscience graduate program, medical student education and an annual symposium. The center's third mission is to educate the public, and it may be best known off-campus for its popular, free Neuro Night sessions on such topics as Alzheimer's Disease, the brain and infections, autism and the healthy aging brain.

For undergraduates and high school students interested in attending medical school, there is Mini Med School, a popular one-night session first held last fall. For college students that are interested in graduate school, there is the Mini Graduate School. Meet the Professor Breakfasts are scheduled in both the fall and spring, and they are designed to give graduate students the opportunity to question physicians about the clinical aspects of their research. The center's 20th anniversary symposium was held last September and covered multiple aspects of cutting-edge neuroscience research conducted at the OU Health Sciences Center and at research institutions from around the state. Because neuroscience research pushes the envelope on knowledge of the brain - one of science's last and most daunting frontiers - it has become the nexus for discovery of how human experience and biology influence each other. The 100 members of the center represent both OU Health Sciences Center and Norman campuses, plus the Oklahoma Medical Research Foundation. Their research reflects the broad range of scientific studies considered today to be neuroscience, from the search for cures for Alzheimer's and Parkinson's diseases to understanding spinal cord neurophysiology to the neurobiology of addiction.

Greenwood-Van Meerveld's focus for a number of years has been gastrointestinal discovery research, and it has won for her the prestigious Janssen Award in 2004 with its $10,000 prize for advancing the understanding of gastroenterology. In 2006, she received a VA Career Scientist Award for her work related to veterans' health. She also holds the Presbyterian Health Foundation Chair in Neuroscience. Her recent research has centered on understanding the communication between gut and brain so that a way can be found to suppress the pain associated with IBS. "We always thought anxiety worsened the symptomology, that IBS came first and anxiety worsened it," Greenwood-Van Meerveld said, "but our data is suggesting that it might not be a one-way street." "We found a couple of years ago that we could take different strains of rats with various levels of baseline anxiety and see if there are any differences with the GI tracts in these rats. What we found was that the high-anxiety rat had hypersensitive colons - normal events were perceived as painful."

Multiple neurotransmitters, including corticotrophin-releasing factor (CRF) and serotonin (5-HT), are credited for playing a major role in regulating mood, appetite, sleep, emotions and the pathogenesis of IBS, Greenwood-Van Meerveld said. Further evidence of the importance of serotonin came in a recent study of rectal biopsies from IBS patients who were shown to have abnormally low levels of the serotonin transporter (SERT). SERT alters serotonin levels in the gut. While CRF antagonists and compounds acting to inhibit or stimulate serotonin receptors are targets for current and future IBS drug therapies, Greenwood-Van Meerveld is continuing her research into "the disconnect in how the gut and brain talk to each other.

"The information from here to here is not normal," she says, pointing first to her abdomen and then to her head, "so the sensory stuff going up is abnormal, and the pathways coming down also are abnormal." "The combined reduction of inhibitory information with an increase in excitation equals more pain," she said. "It's as if the gut is talking too fast to the brain, too fast and too loud, and in response the brain is having a problem knowing how to interpret the information it receives from the gut via the spinal cord." So Greenwood-Van Meerveld is looking at the amygdala, "where ultimately the shouting - the hypersensitivity - may be stopped or dampened."