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Sex, gender, and the brain: Promoting Equity for Excellence

In 2012, Dr. Jeffrey Mogil piqued the science community’s interest in an issue of Nature Reviews Neuroscience. He observed that most patients with chronic pain are women. However, it is difficult to determine whether this sex difference corresponds to differences in pain sensitivity. Fast forward a couple of years. His quest for answers on how women and men experience chronic pain stuck.

Dr. Mogil and his colleagues received a 2014 Brain Canada Multi-Investigator Research Initiative (MIRI) Team Grant from Brain Canada to further their research on sex differences in chronic pain by searching for sex differences in brain functions using imaging techniques in mice.

Jeffrey Mogil, Ph.D.

Dr. Mogil returned to Nature Neuroscience in 2015 with a study carried out by labs in Montréal and Toronto, led by him and Dr. Michael Salter, where researchers interfered with microglia functioning and found striking sex differences. While blocking microglia functioning reduced pain in male mice, it had no effect on pain transmission in female mice. An entirely different type of immune cell, likely the T cell, appears to carry out this function in females.

“Sex differences have been almost entirely ignored in pain research, because pain research has been performed primarily on male rodents,” says Dr. Mogil. “The research, supported by Brain Canada, showing sex specificity of immune cell mediation of pain hypersensitivity in the spinal cord, is one of the more striking examples to date of qualitatively different biological underpinnings of a phenomenon experienced by both sexes.”

The same quest for answers motivates Dr. Nicole Gervais at the University of Toronto. Dr. Nicole Gervais and her research colleagues at the Einstein Lab, funded by Brain Canada and the Alzheimer’s Association through the Alzheimer’s Association Research Fellowship, study how the loss of estrogen due to natural or surgical menopause affects sleep, cognitive function, brain inflammation and brain structure. The results could shed new light on how hormones and genetics may interact to promote Alzheimer’s risk, possibly through effects on sleep and brain inflammation. A better understanding of these biological mechanisms could suggest ways to reduce risk or develop targeted treatments to slow or prevent Alzheimer’s disease.

With projects such as those led by Dr. Mogil and Dr. Gervais, Brain Canada wants to raise awareness about the importance of conducting research that is sensitive to sex and gender differences. That is why we ask researchers applying for grants to describe how sex and gender are taken into consideration in their research project. Our commitment extends to gender parity. While 49% of the applications received for our last three major competitions announced in 2018 were submitted by female researchers, 57% of the recipients were women.

Furthermore, Brain Canada’s partnership with the Women’s Brain Health Initiative (WBHI), which began in 2016, has been transformative. As part of the partnership, Brain Canada has sponsored editions of the WBHI magazine Mind Over Matter focused on sex and gender and prevention of age-related cognitive decline. Brain Canada and WBHI have also co-organized 12 Millennial Minds events in Toronto designed to educate young Canadians on the importance of brain health and gender- based brain-aging disease research.

“Ensuring that women’s voices are heard and celebrated in research is not only about equity; it is also about excellence”, said Inez Jabalpurwala, President and CEO of Brain Canada.