University of Guelph professor Ray Lu researches stress at the molecular level.

Stress is a natural biological process enabling us to deal with the world around us. In short bursts, such as exercise or watching a thrilling film, stress is beneficial to the body. But when stress is too much or lasts too long, the effects can be detrimental to our health.

New research by University of Guelph professor Ray Lu, Department of Molecular and Cellular Biology, sheds light on the molecular basis of our sensitivity to stress, paving the way for possible new treatment options.

At the molecular level, the mechanics of stress response are complex, employing the immune, metabolic, endocrine and nervous systems. In addition, the type of stress may alter how the body uses these different processes. For this reason, figuring out how to deal with the complications of stress has remained a challenge.

The most studied molecular lynchpins of stress have been hormones — among the most well known is glucocorticoid (GC), known as cortisol in mammals.

Lu’s research has also worked to better understand the role of a gene called Luman in ensuring the cell properly responds to stress. In a new study published in the journal Molecular and Cellular Endocrinology, Lu reveals that Luman is critically important in the regulation of the GC response in the body.

Along with psychology professor Elena Choleris and biomedical sciences professor Neil MacLusky, Lu worked with a mouse strain in which the Luman gene was disabled, and compared it to mice with normal gene function.

The researchers performed several behavioural tests on the mice, including one that offered the option of crossing an open-ended beam or a closed beam with hiding places at both ends. “Mice are prey species, so they should naturally avoid any open space,” says Lu. Instead of choosing the closed beam for safety, the mice with disabled Luman became the “equivalent of human daredevils” and lingered on the edge of the open beam.

The results showed the mice with disabled Luman were unable to secrete the stress hormone cortisol, resulting in less anxiety and stress.

Lu is now working with colleagues at the Ontario Agricultural College and the Ontario Veterinary College to apply his research to the selection and breeding of low-stress farm animals, and to improve their well-being and immunity while reducing the use of antibiotics.

Lu says human applications of this research could include screening people working in high-stress jobs — such as paramedics, police and soldiers — who may be more sensitive to stress and more susceptible to developing mental health conditions, including post-traumatic stress disorder. This could lead to improved preventive measures and treatments.

“The key issue is to reduce, monitor or manage the sensitivity to stress,” says Lu. “It would be nice if we could come up with some kind of pharmaceutical intervention to fine-tune these particular signaling pathways. For people who have too low of a stress response, we could boost it. For those who have too high of a stress response, we could suppress it.”

With contributing writer Jason Tetro.