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Trailing a mystery: why do we reject food?

Released: Thursday, December 16, 2004

When airplane pilots face an emergency, they go on "automatic," working through a series of procedures to recover control. Our bodies often do the same thing when we are sick, trying a series of changes that includes hypersensitive skin (painful to the touch), increased body temperature (fever), increased fatigue or sleepiness, loss of appetite and nausea. Each bodily change has a potential role in recovery: sensitive skin and fatigue prompts us to remain still and sleep, conserving energy reserves to fight off infection; fever can impair the reproduction of the pathogen; and nausea may lead to vomiting. The nausea will prevent us from ingesting more of the possible cause of the illness (for example, spoiled food, bacteria or other toxic substance) and the vomiting will help us get rid of the source.

This collection of physiological responses is the result of a fascinating and highly complex set of signals passed between the immune and nervous systems. Chemicals produced by our immune system trigger these responses. These circulating signals allow the brain to detect infection, disease, or toxins anywhere in the body and to muster a massive counter attack, commanding various systems and organs to get in the fight.

Inborn survival instincts, such as the drive to eat, are extremely strong. Therefore, researchers are quite interested in how so many, and diverse, diseases can shut down that drive, particularly when it may be harmful in the long run. Seriously ill patients, especially the terminally ill, can actually waste away quickly through lack of nutrition as their bodies close down and reject eating.

True to Pennington Biomedical Center's mission "to promote healthier lives through research and education in nutrition and preventive medicine", the husband and wife team of Dr. Richard Rogers and Dr. Gerlinda Hermann have been investigating the cause of the disease related shutdown of gastro-intestinal processes. Although they have been working for more than 20 years together investigating the neural circuitry involved in the normal control of gastric function, within the last 10 years they have been able to demonstrate that there is cross-talk between the immune and nervous systems during disease states.

One of the chemicals made early in the immune response is called tumor necrosis factor (TNF; this is a deceptive name in that TNF does not actually cause necrosis of tumors). Under circumstances where TNF levels are elevated (such as disease, infection, cancer, or radiation therapy), nausea and vomiting are often associated.

Rogers, Hermann, and their laboratory have been able to demonstrate that this circulating chemical from the immune system, TNF, is able to access that part of the brain that is responsible for controlling gastric function. Its ability to shut down normal gastric function, which is perceived as nausea, is extremely powerful. Their experiments also indicate that TNF may be affecting the neural circuitry involved in the perception of touch and pain. These observations would help explain the hypersensitivity to touch that we experience when we are ill.

At this point, one might be tempted to suggest that all we need to do to turn off the production of TNF to relieve these symptoms of nausea, vomiting, and sensitivity to touch. However, we need to take into account what beneficial roles TNF may have. During the 1950s, it was fairly common practice to prescribe the sedative thalidomide to pregnant women that were having difficulty with "morning sickness". The thought was that these women were anxious about the pregnancy and the "sedative" relieved these symptoms. Unfortunately, these women ultimately gave birth to children with horrific birth defects primarily affecting the limbs or the total absence of limbs. Only recently was it determined that thalidomide disrupts the production of TNF! Developmental studies have shown that TNF is quite elevated during pregnancy and plays a critical role in the development of blood vessels and, ultimately, the development of limb buds. The work by Rogers and Hermann on the role of TNF and gastric function now completes the story about the relationship between morning sickness, thalidomide, and birth defects.

Clearly, turning off the production or action of TNF completely may have detrimental effects we are yet discover. Therefore, the next task for this research team is to understand the details of how and where TNF works within the nervous system. This information will lead to other, specific therapeutic targets.

Now the challenge focuses at the cellular level to study the messaging network used by TNF. These studies require creative experimental designs, sophisticated technology, and a highly specialized microscope. With the generous funds that the Pennington Biomedical Research Center offered, Rogers took a daring step and purchased one of these specialized laser microscopes and combined several techniques used by other sciences to get a closer look at the neural circuits. Molecular "dyes" are used to visualize the activity induced by TNF in individual brain cells.

The price tag for such technology? Rogers says you might get an "off-the-shelf" device for about a quarter million dollars. So goes the cost and the pace of cutting edge research. Rogers says that, "No one else is doing this sort of work in this area of the brain,"

So why is the work important? According to Rogers, "In these days of rapid advancements in treatment, if you can buy a terminally ill patient more time through continued nutrition, he or she might live to see a permanent, life-saving treatment."

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The Pennington Biomedical Research Center is at the forefront of medical discovery as it relates to understanding the causes of obesity, diabetes, cardiovascular disease, cancer and dementia. Itis a campus of the Louisiana State University System and conducts basic, clinical and population research. The research enterprise at the Center includes approximately 80 faculty and more than 25 post-doctoral fellows who comprise a network of 50 laboratories supported by lab technicians, nurses, dieticians, and support personnel, and 19 highly specialized core service facilities.  The Center's more than 500 employees perform research activities in state-of-the-art facilities on the 234-acre campus located in Baton Rouge, Louisiana.