Are Environmental Toxins Causing Disease by Disrupting Our Circadian Rhythms?

Disruption to our innate circadian rhythms, or biological clocks, has been linked with a wide range of human disorders. New studies with the tiny aquatic zooplankton Daphnia raise the question of whether human circadian rhythms might be affected by the environmental toxins to which we are exposed every day. The research, by a team at Rensselaer Polytechnic Institute, found that circadian rhythms were significantly disrupted in Daphnia that had adapted to environmental pollution from road salt and that this disruption may occur at the level of epigenetic changes to key clock genes.

“This research shows that exposure to environmental toxins may be depressing the function of our circadian clock, the disruption of which is linked to increased rates of cancer, diabetes, obesity, heart disease, and depression,” said lead scientist Jennifer Hurley, Ph.D., an assistant professor of biological sciences, a member of the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer Polytechnic Institute. “This is the first time anyone has shown this happening at the level of the core clock, which we had considered to be heavily buffered against these types of environmental effects.”

The studies are reported by Dr. Hurley, and colleagues Kayla D. Coldsnow and Rick A. Relyea, Ph.D., in a paper in Ecology and Evolution (“Evolution to Environmental Contamination Ablates the Circadian Clock of an Aquatic Sentinel Species”).

The research is founded on recent work by the Jefferson Project at Lake George, which indicated that while Daphnia pulex can rapidly evolve tolerance to pollution by road salt, this adaptation may come at a cost, with the organisms suffering from disruption to their natural circadian rhythms. “Plankton, which are key consumers of algae and a food source for many fish, may be making a monumental tradeoff to tolerate increased road salt,” said Dr. Relyea, Jefferson Project director, CBIS member, and co-author of the study. “The circadian rhythm guides these animals through a daily migration, to deep waters during the day to hide from predators and shallow waters at night to feed. Disrupting that rhythm could affect the entire lake ecosystem.”

And because Daphnia are a common model for investigating how organisms respond to environmental stress, environmental toxin exposure may feasibly also impact on higher organisms. “This suggests that higher eukaryotic clocks, such as those found in humans, may be affected by the adaptation to pollutants at the level of the core oscillator,” the researchers write. 

To investigate the effects of salt on circadian rhythms in Daphnia, the CBIS team first looked at the changing expression levels of a core set of circadian clock genes, including the gene period, or per, which is also a core clock gene in another model organism, the fruit fly Drosophila melanogaster. They first showed that per mRNA expression oscillated with a 24-hour rhythm in Daphnia that were exposed to naturally low salt levels and were kept constant dark conditions. This gave a clear indication that the organism did have a functional circadian clock.

To test whether adaptation to high-salt environments affected this functional circadian clock, the researchers carried out a similar experiment with five populations of Daphnia that had previously adapted to differing levels of salinity. The results showed that per mRNA expression rhythms deteriorated in parallel with adaptation to increasing salt concentrations. In effect, the natural rhythm of per mRNA expression was inhibited by high levels of salinity. “…populations adapted to high NaCl concentration exhibited an ablation of period oscillation,” the researchers write. Interestingly, the expression of other genes was increased as part of the Daphnia populations’ responses to salt adaptation, but of all the genes they looked at, only per was repressed in response to salt adaptation. “These results suggest that rapid evolution of salt tolerance occurs with the tradeoff of suppressed circadian function.”

Having identified which circadian clock gene is suppressed by adaptation to salt levels, the researchers then queried the mechanism that underpins per gene inhibition. They note that previous research in another Daphnia species, D. magna, had shown that exposure to NaCl led to significant increases in DNA methylation, implicating the involvement of epigenetic changes. Other research had also shown significant differences in the expression levels of many genes between salt-tolerant and salt-intolerant D. pulex.

“This indicates that epigenetic changes may be involved in the evolution of salt tolerance and, by extension, the disruption of the circadian clock,” the team notes. “What we see is a graded, measured response in this organism,” Hurley said. “…the higher the level of salt to which the Daphnia are adapted, the more it suppresses the expression of its circadian clock. The population adapted to naturally low salt levels exhibits a beautiful, healthy oscillation in per mRNA expression, but the population adapted to high salt levels has completely lost its ability to oscillate this mRNA expression.”

The reported studies also only consider one toxin in fresh water. Many other contaminants, including pesticides, pharmaceuticals, and heavy metals, are becoming increasingly common, they comment. “This suggests that our research demonstrating circadian rhythm disruption from chemical contamination and its proposed physiological, psychological, and behavioral consequences may just be the tip of the proverbial iceberg,” the authors suggest.

The circadian clock appears to be conserved between Daphnia and higher eukaryotes, indicating that disruption of this clock by environmental toxins may affect circadian rhythms in other species “This suggests that higher eukaryotic clocks, such as those found in humans, may be affected by the adaptation to pollutants at the level of the core oscillator,” they conclude.

“The implications are substantial,” Hurley asserted. “You've exposed Daphnia to an environmental toxin, and its clock was suppressed, probably through epigenetic mechanisms. The clock and biology of Daphnia are very similar to the clock and the biology both in our brains and most organisms. Is it possible that we can see epigenetic changes in the human brain because of exposure to environmental toxins?”