Toxicant-Triggered Anxiety

Juvenile fish exposed to a common environmental toxicant show signs of anxiety.

Published May 1, 2017

When you plunk an adult zebrafish into an unfamiliar tank, it will behave predictably: the small, striped, freshwater minnow freezes for up to a minute, slowly begins to explore the tank, and then, when it’s good and ready, swims around as if it’s been there the whole time. The zebrafish’s literal test of the waters is a survival instinct that directs the fish to proceed with caution.

Yet adult zebrafish that were born in water contaminated by a common class of toxicants—polychlorinated biphenyls, or PCBs—have a much more hesitant reaction. In new research, Neel Aluru, a biologist at Woods Hole Oceanographic Institution, shows how fish that were exposed to PCBs during development take much longer to habituate—they seem to be stuck in proceed-with-caution mode. It’s the fishy equivalent of generalized anxiety disorder, Aluru says.

Aluru specializes in epigenetics, the study of how an organism’s environment manipulates the expression of its genes. In response to environmental cues—everything from toxic substance exposure to dietary factors to changes in air temperature—genes can be turned on or off.

“We have the same number of genes in every cell in the body, but epigenetics is the reason why all cells have their own specialization: skin cells are different than heart cells, which are different than brain cells, and so on,” says Aluru.

Differences in chemical factors cause cells to specialize, but epigenetic effects operate more broadly. Environmental cues, such as exposure to toxic substances or a change in temperature, can cause even fully developed organisms to change their physical appearance or behavior. Consider the recent discovery of climate-related epigenetic change in mammals: wild guinea pigs living in high-heat enclosures produce offspring with body-temperature-regulating genes significantly different than animals living in ambient-temperature enclosures. Similar climate-related epigenetic changes have been seen in shrimp and plants. Epigenetic adaptations to high-heat environments are largely beneficial, but epigenetic changes are not always positive—they’re also responsible for the anxiety in PCB-exposed zebrafish, Aluru says.

Many countries, including Canada and the United States, have banned or restricted PCBs, a family of 209 chemicals found in industrial products such as paints and coolants. Yet they are still present in the air, water, and soil—particularly in coastal waters, which are repositories for PCBs shed from marine paint, and in ecosystems close to factories that manufactured PCB-containing products. Even decades after they were banned in the United States (in 1979), scientists continue to detect PCBs in people, fish, birds, and even plants.

Aluru studies one of the most potent PCBs, PCB-126, which in acute doses causes liver damage, skin lesions, and respiratory issues in humans, and a host of other issues in animals, from cancer to hormone problems.

But the fact that we humans share 70 percent of our genes with zebrafish, and that 84 percent of human genes associated with diseases have a zebrafish equivalent, has Aluru wondering whether people may be susceptible to the anxiety-linked behaviors caused by PCBs.

Aluru’s goal is to understand how low-level PCB exposure during embryonic development can cause physical, behavioral, and molecular changes later in life—something that hasn’t previously been studied in humans or animals.

Besides observing delayed anxiety-like behaviors in adult zebrafish, Aluru has also found molecular differences in the brains of developing fish. “This suggests genetic changes that materialize later in life are programmed at the time of exposure,” he says.

While some may criticize animal studies like Aluru’s as a poor substitute for human studies, University of Illinois neuroscientist Paul Eubig says work like this can offer a better understanding of the epigenetic effects of toxicant exposure during development.

Eubig, who has studied the link between PCB exposure and attention deficit hyperactivity disorder speculates that future research will focus more and more on how environmental toxins cause their epigenetic effects.

“We are familiar with the effects of PCBs on the brain and body,” says Eubig. “Now we need to know how PCBs’ effects occur on a molecular level—research like Aluru’s is helping to achieve that.”