A creature that "resembles a wet brown paper bag with the appetite and table manners of a hyena" is helping researchers blaze a trail toward future pharmaceutical treatments for depression and other disorders. Researchers at Illinois are studying two species of marine mollusks to learn more about the chemical pathways of serotonin in the human nervous system.
"Understanding novel serotonin pathways in a tissue-dependent manner is useful for the development of pharmaceuticals intended to preserve serotonergic signaling," says Jeffrey N. Stuart, a doctoral student in the Department of Chemistry .
Serotonin is a neurotransmitter present throughout the body. When the nerve cells that contain it are activated, serotonin is released. The neurotransmitter travels and stimulates other nerve cells, enabling their messages to spread through the nervous system.
"When serotonin is released, you do not want its signal to last forever," sayes Jonathan Sweedler, a professor of chemistry and Stuart's academic adviser. The signal caused by serotonin is turned off by enzymes that inactivate it by converting it into various metabolites, such as the ones discovered by Stuart.
Disruptions of serotonin signaling pathways are thought to occur in disorders such as depression, anxiety, sudden infant death syndrome, attention deficit hyperactivity disorder, and irritable bowel syndrome. Many pharmaceutical treatments restore the pathways by preventing the cellular uptake of serotonin, where it is converted to other metabolites, or by directly inhibiting the enzymes responsible for the molecular conversion. Pharmaceuticals intended to correct serotonin imbalances in a specific tissue, such as in the brain, ultimately take effect in other tissues as well. That potentially leads to unwanted side effects.
Stuart, using a detection system built to measure serotonin and related compounds, found two new serotonin metabolites in the nervous system of marine mollusks. The metabolites were in separate yet adjacent body tissues, suggesting, he says, that different chemical pathways exist to convert serotonin.
Marine mollusk species Aplysia californica and Pleurobranchaea californica that were used in these experiments are considered to be ideal model systems to study serotonin. Although mollusks have simpler nervous systems than mammals, they show mammal-like qualities that influence behavior, such as learning and memory. Each one "resembles a wet brown paper bag with the appetite and table manners of a hyena," says Rhanor Gillette, professor of molecular and integrative physiology . He collaborated with Stuart and Sweedler to study how serotonin metabolites relate to behavior.
Stuart and Jason Ebaugh, a doctoral student in the neuroscience program, measured the blood levels of serotonin sulfate as a time-of-day function. It may be important for growth, most of which occurs during sleep, Gillette says. It's possible that the role of serotonin sulfate in marine mollusks is similar to melatonin, which resests the circadian clock in humans.
"This is the first quantitative measure of how serotonin metabolites are related to a behavioral state in marine mollusks," Sweedler says. "What we do not know is whether serotonin sulfate causes the behavior or whether the behavior causes the elevation of serotonin sulfate."
Other contributors to the research are Leah Squires, Elena Romanova, Jennifer Jakubowski and Xin Zhang, all doctoral students in the Department of Chemistry; postdoctoral fellows Stanislav Rubakhin and Nathan Hatcher, both in chemistry; and undergraduate biochemistry major Ashley Copes. The National Institutes of Health funded the research. Stuart also was supported by an American Chemical Society fellowship.
