Clues for stress resilience found at the blood-brain barrier

What factors promote resilience to stress? Researchers have investigated this question at the level of neurons for decades, but Dr. Caroline Ménard found an answer where the blood system and the nervous system interact, the blood-brain barrier (BBB).

Her work shows that social stress alters the BBB and that non-neuronal cells are involved. Specifically, Dr. Ménard studies the role of non-neuronal cells called astrocytes, which are star-shaped cells that line the BBB like a fence.

“We don’t only feel emotion in our brain; we feel it in our gut, we feel it in other systems. That’s why we study the blood-brain barrier – it connects the brain with the immune system, with the vascular system, and with all the hormones that circulate in the blood. Our understanding of those interconnections and their influence on health is advancing, and we’re developing tools in the lab to facilitate that.”

Dr. Caroline Ménard, Azrieli Future Leader in Canadian Brain Research

Dr. Ménard and her research team looked at a receptor on astrocytes that plays a role in mediating the levels and activity of neurotransmitters.

Using a new tool developed in their lab, the team was able to overexpress this receptor in mice. When these mice were put under stress, they showed less anxiety- and depression-like behaviours compared to the control group.

Stress-induced changes occurred in different brain areas in female versus male mice, which indicates that astrocyte function might be altered in a sex-specific manner.

Dr. Ménard’s findings suggest that astrocytes play an important role in stress response and possibly, human depression, via their position lining the BBB.

What’s the impact?

In any given year, 1 in 5 people in Canada will personally experience a mental health problem or illness. Prolonged exposure to stress is one of the factors that can lead to mental illnesses.

By advancing our understanding of stress resilience at the biological level, Dr. Ménard’s work sparks new thinking on how to prevent mental illnesses like anxiety and depression.

Her work also accelerates scientific practice; Dr. Ménard had no experience working with astrocyte receptors prior to her Future Leader grant, but now she and her team are receiving inquiries from researchers around the world for access to the tools they’ve developed to manipulate them.

Since launching her independent academic career, Dr. Ménard’s laboratory has published in highly prestigious journals including Immunity, Nature Communications, PNAS, Neuron, Trends in Neuroscience, Biological Psychiatry, Nature Biomedical Engineering, Journal of Clinical Investigation, etc. The discoveries have been transformative as they identified novel barrier-related mechanisms underlying stress resilience vs susceptibility but also predictive blood biomarkers of disease vulnerability, paving the way to precision medicine by highlighting sex differences in the signature of brain disorders. Most recently, she was recognized with the Canadian Association for Neurosciences 2024 New Investigator Award.

More on Dr. Caroline Ménard’s research

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