MDI Biological Laboratory

Coffman Lab Awarded $449k for Collaborative Research on Arsenic and Depression

  • April 9, 2024

Using zebrafish to find links between early-life exposure and later effects

Arsenic exposure from well water and food is a major public health concern, while prenatal exposure to low levels of the substance heightens the risk of developing psychiatric disorders such as depression and anxiety in adulthood.

The MDI Biological Laboratory’s James A. Coffman, Ph.D. and colleagues have been researching the effects that arsenic exposure has on the immune system of zebrafish, which is one of the Laboratory’s models for human health. Now they plan to build on that data to examine how early-development arsenic exposure may interfere with specific signaling pathways in ways that lead to nervous system inflammation that promotes psychological or behavioral disorders.

Their prime suspect: a group of hormones called “glucocorticoids” that the body sends out in response to stress, causing a cascade of varying physiological effects. Dysregulation of that system, Coffman says, can have long-term psychological consequences as well.

“We’ve known that a lot of these disorders, major depression, for example, are due to neuro-inflammation, inflammation of the brain,” Coffman says. “And we can model that in zebrafish, which share all the relevant genes and signaling pathways with us.”

In March, Coffman won a two-year grant for the work, after responding to a call by the National Institutes of Health for projects to connect environmental exposures and psychiatric disorders. The award by the NIH’s National Institute of Environmental Health Sciences, totals $449,000.

Coffman will collaborate in the grant research with Michael Burman, Ph.D., professor of psychology and Academic Director of the University of New England’s School of Social and Behavioral Sciences, and Erik Duboué, Ph.D., a neurobiologist at Florida Atlantic University.

The team will expose zebrafish embryos to low levels of arsenic that correspond to what humans may experience in the prenatal environment, including in Maine, where arsenic in residential well water is a known threat. They will document the zebrafish’s later-life responses – watching for specific behaviors, such as slow swimming, excessive or blunted startling, and swimming close to tank walls, that are stand-ins for psychobehavioral disorders in humans.

“These are behaviors that zebrafish can engage in, in response to stressors that we can relate to depression, for example, or anxiety,” Coffman says. “We’re also going to look at how exposure to low levels of arsenic affects the development of the brain in zebrafish, focusing on areas that are involved in behavior regulation. We’ll look for markers of inflammation and disruptions in glucocorticoid receptor signaling.”

Ultimately, Coffman says, the work could lead to new insights about the molecular mechanics of how chronic early life exposure to low level arsenic increases risk for developing psychological disorders, and about what are safe or unsafe levels of arsenic in human water and food supplies.

Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number R21ES035818