Health | Researchers from UFRGS and France’s Pasteur Institute observed that a reduced level of the GDF11 protein in the body during depression is responsible for lapses in memory and concentration by compromising the disposal of inactive cell debris
*By Alexandre Briozo Gomes Filho
*First published April 27, 2023
*Photo: Flávio Dutra/JU archive. Jul. 12. 2008
In recent years, depression has become more prevalent all over Brazil. According to a study by the Health Ministry published last year, around 10% of Brazilians were diagnosed with the disease in 2021. Achieving significant progress for studies on the causes, impacts and treatments of the disease, a group of researchers from Brazil and France concluded that a rejuvenating protein called GDF 11 is reduced during depression, and such depletion is linked to the loss of concentration and memory, as well as to the accelerated aging observed in the disease. The reduction of this protein affects both neurogenesis (the formation of neurons) and autophagy, a catabolic process that cleans the residual structures and proteins in cells — neurons, in this case.
In this study, whose results were published in Nature Aging, Flávio Kapczinski, faculty member of the department of Psychiatry and Legal Medicine of UFRGS, worked together with a group of researchers from the Pasteur Institute in France. The scientists observed that, in cases of depression or during the depression phase of bipolar disorder, a flu-like inflammation occurs throughout the body. Seeking to understand the effects of this condition, they observed that the more often a person is depressed or the longer the disease lasts, the more severe the inflammation is. Considering that someone who is depressed for a long time invariably begins to develop concentration and memory problems, the researchers linked these constraints to the inflammatory condition and, in turn, associated the latter with the reduction of the GDF11 protein.
“In depression, it is as if you grew older faster: we call it accelerated aging. Since the researchers at Pasteur had linked this molecule [GDF11] to a rejuvenating effect, we considered the following hypothesis: what if in face of inflammation a reduction of this rejuvenating molecule also happened? This led to our research.”
Flávio Kapczinski
Carried out using a translational methodology, in which laboratory experiments are conducted with animals and humans, the researchers, using the ELISA method (a methodology based on antigen-antibody reactions that are detectable by means of enzymatic reactions), injected mice with corticosterone, a stress hormone, inducing the animals to a depressive behavior. By measuring the mice’s GDF11 levels, the researchers found that the protein had been reduced. When GDF11 was replaced, rodents stopped displaying depressive behavior.
When the GDF11 level of young persons diagnosed with depression was measured, researchers found that it was also reduced, indicating that the accelerated aging of depressed persons happens even if they are still young.
A lasting and thorough process
Every work has its challenges. Among the difficulties faced by professor Kapczinski and his fellow researchers, the slow pace of the study was the biggest one. A total of 18 experiments were carried out between 2018 and 2023, with the study being concluded in February. Kapczinski adds that the P.h.D. completion and consequent departure of doctoral students who were participating in the study was also a problem. “It took so long the researchers lost motivation. We had to keep ourselves on our toes, doing each experiment little by little,” he says. As to the departure of post-doctoral students, the maintenance of a center with all data organized by the researchers throughout the study was essential to preserve research information.
This delay in the study was because Kapczinski’s team needed to show the mechanism by which the process – which is gradual – happens. In other words, they needed to show that GDF11 levels were low during depression and that by replacing the protein in patients’ organisms, their depression ended due to autophagy. “We initially hypothesized that the protein would be low during depression and that, as soon as we provided it back, the depression would be lessened. But we had no idea this would happen via autophagy. We had to test several other mechanisms until we isolated the one responsible for autophagy,” Kapczinski reports. This explanation was needed for the study to be published in Nature Aging.
Extending the studies on GDF11
The researchers still do not know if the study will result in the finding of a new treatment against depression. They intend to study a new treatment based on the effects of GDF11, aimed at counteracting the memory issues faced by patients, which, according to the latter, are not solved by current treatment methods. Moreover, there is still doubt as to whether the protein can be administered to humans, given that it might cause allergies.
Continuing his work on the mechanisms of depression and bipolar disorder, aimed at the discovery of new treatments, Kapczinski is carrying out a study to verify whether dementia can also result from a deficiency in the GDF11 protein. “Measuring the level of this protein in patients with depression and dementia is an ongoing process that’s been carried out for many years now,” he says.
Translated into English by Daniel Senna Irgang, undergraduate student enrolled in the course “Supervised Translation Training II (English)” of the Undergraduate Program in Language and Literature, under the supervision and translation revision of Professor Elizamari R. Becker (P.h.D.).