Jim Coffman, Ph.D., Delivers a Work-In-Progress Report
MDI Biological Laboratory associate professor James A. Coffman, Ph.D., recently delivered a summary of research being conducted in his laboratory on the effect of stress on health at a recent Work in Progress (WIP) presentation to the MDI Biological Laboratory staff. Faculty members regularly deliver such presentations in order to share knowledge, promote collaboration and keep staff up-to-date on their research.
Research conducted by Coffman, a developmental biologist, and research assistant Elli Hartig in zebrafish is identifying how the genetic pathways that regulate the activity of the immune system are affected by chronic stress experienced early in life. The research found that zebrafish larvae exposed to the stress hormone cortisol – an important physiological regulator of inflammation – for only the first five days of development gave rise to adults that displayed diminished control of inflammation. Uncontrolled inflammation has been linked to a variety of age-related degenerative diseases. The adult zebrafish developed from larvae exposed to cortisol also demonstrated an impaired ability to repair and regenerate tissue in response to injury.
Coffman’s research is consistent with a growing body of evidence indicating that exposure to stress early in life – even for a very brief period – can lead to lasting effects on health. In short, as he put it in the presentation, the fish exposed to cortisol early in life were “stressed all the time.” “This has astonishing socioeconomic implications,” he said. For instance, it could help explain why children – and even fetuses – that experience chronic stress as a result of low socioeconomic status, an abusive emotional environment or poor nutrition are more vulnerable to disease later in life. The pro-inflammatory state observed in the adult zebrafish that were exposed to cortisol as larvae could lead to degenerative diseases such as arthritis, cancer and heart disease, as well as to aging itself.
While a pro-inflammatory state may confer advantages in a young organism – by enhancing the ability to fight infection following injury, for instance — it can be harmful over the long term. “The adult zebrafish exposed to cortisol early in life had higher levels of cortisol as adults even when they were unstressed,” Coffman said. “The immune genes were being regulated in the opposite way from what we would have expected.” In effect, the exposure in early life programmed them to be more susceptible to inflammatory disease. Coffman’s lab is continuing to study how the zebrafish genes that control responses to stress, which are shared by humans, are regulated. In particular, they will be looking at the question: “What are the molecular changes induced by chronic early life stress that cause aberrant regulation of immune genes and inflammation in adulthood?”
The identification of the genetic pathways governing aberrant responses to stress raises the prospect that therapies may one day be developed that can mitigate the damage caused by exposure to stress at an early age.