An international research team has identified a protein that reduces depression-like symptoms and reverses memory decline in aged mice. The protein, known as growth differentiation factor 11 (GDF11), appears to stimulate key cellular processes that protect brain cells from damage. The team also found significantly reduced levels of GDF11 in humans among those experiencing depression compared to a healthy control group.
The study was recently published in the journal Nature Aging.
The findings highlight the reliability of GDF11 as a biomarker for depression and a potential pathway for a new antidepressant treatment.
Dr. Flávio Kapczinski, study co-author and professor emeritus in the department of psychiatry and behavioural neurosciences at McMaster University, described this study as the most important in his career.
“It is very rare in psychiatry to describe a new mechanism of psychopathology, and to show the biological pathway and the molecular target,” Kapczinski said. “We achieved all of that in this paper. We are thrilled.”
Researchers linked GDF11 to neuronal autophagy, a natural process that protects brain cells from damage. Reduced neuronal autophagy is associated with accelerated aging and decreased longevity. The study team found that GDF11 reactivates key proteins regulating autophagy that are known to be compromised in patients with major depressive disorder.
The international study included researchers from the world-renowned Pasteur Institute in France; McMaster University and St. Joseph’s Healthcare Hamilton in Canada; as well as several partner institutions in Brazil.
Two separate analyses were conducted for the human portion of the study, which was based on a large Brazilian cohort study of young adults. Researchers identified young adults with major depressive disorder, as well as those presenting with a current depressive episode. Compared to healthy control groups, both analyses found that GDF11 was significantly decreased in those experiencing depressive symptoms.
Human blood samples from the study groups were analyzed at the Centre for Clinical Neurosciences (CCN) in Hamilton, Ontario. The CCN – a partnership between St. Joseph’s Healthcare Hamilton and McMaster University – is a research hub for psychiatry and behavioural neurosciences that operates a state-of-the-art wet lab at St. Joe’s West 5th campus.
In April, researchers from the CCN will present their findings at a neuroscience symposium hosted by the Pasteur Institute in Paris, France. The team will also discuss the next steps in their ongoing collaboration. (See “The French Connection: Forging new partnerships in neuroscience” on page 6 of The Research Institute’s 2019 Annual Report for more details on the international partnership.)
Funding for the study was provided in part by the Strategic Alignment Fund at McMaster University and by St. Joseph’s Healthcare Foundation.