Glial Cells as Enhancers of Depression Treatment

Astrocytes are not actual nerve cells, but cells supporting the nerve cells. They clear metabolic waste from the brain, while also affecting nerve cell connections in the brain. Astrocytes help the brain create new connections between nerve cells and, accordingly, remove the connections the brain no longer needs.

“Depression is humanity’s most common mental health disorder that affects the lives of millions of people. Based on preliminary studies, it seems that antidepressants affecting the functionality and quantity of astrocytes could serve as a new and fast treatment for depression. Patients suffering from depression seem to have fewer astrocytes than other people, but more detailed studies on the connections between astrocytes and depression are still needed,” says Marko Rosenholm, Postdoctoral Researcher at the University of Copenhagen.

Rosenholm, who graduated as a Doctor of Pharmacy in 2020, has been researching rapid-acting antidepressants and their effect on the brain for several years. In 2023, the Instrumentarium Science Foundation awarded him a post-doc grant amounting to €65,000 for his research “The effect of astrocytes on synaptic plasticity against the background of rapid-acting depression treatments”.

New rapid-acting depression treatments are needed

Traditional antidepressants work for about one-half of depressed patients, but not for all. The rapid-acting depression treatments currently administered include, for example, electrotherapy and ketamine, which is also used as an anaesthetic. They bring relief to many people and are used as a last resort with patients in whose case traditional antidepressants have proven to be inefficient. However, electrotherapy or ketamine are not easily accessible for patients. According to Rosenholm, ketamine has great potential, but comes with the risk of abuse. Because of this, it is not well suited for pharmacy distribution.

“In my research, I examine the effects different antidepressants have on the functioning of the brain and whether new mechanisms that would help in the treatment of depression are out there. From the viewpoint of the research, finding and mapping all the key mechanisms that could be influenced to develop new forms of treatment is of the greatest importance. Astrocytes seem to be a factor whose mechanisms of action on the brain and depression are not yet fully known,” Rosenholm explains.

The research is only in its early stages, so according to Rosenholm, new drugs or treatments related to astrocytes will not be available in the next few years.

Are brain plasticity and depression related?

In the past, astrocytes were mainly seen as the “janitors” of the brain, sweeping away metabolic waste from the brain’s nerve cells. Recently, clear evidence has emerged suggesting that astrocytes affect brain function more broadly. They regulate the blood circulation of the brain and the connections between synapses. This influences the plasticity of the brain, i.e., its synaptic plasticity.

“The plasticity of the brain, in other words, its ability to change, as well as the ability of the nerve cells to create new connections seem to be affected by both older and newer depression treatments. Plasticity is the highest in young children, but reduces with age. The plasticity of a depressed person’s brain is often significantly disturbed. The depression could be rooted in long-lasting stress, for example, which can create a cycle that feeds negative thinking. With treatments or medicines that increase plasticity, it is possible to tune the brain into a state in which this cycle can be broken. In combination with psychotherapy, for example, an opposite positive cycle can be achieved,” Rosenholm describes.

“In my research, I seek new substances and methods by which astrocytes could be employed to maintain and promote the well-being of the brain better than currently possible.”

Top experts return to Finland

According to Rosenholm, the Instrumentarium Science Foundation has a good reputation among researchers. Grants can be applied for even for a thesis and funding is available for a wide variety of research projects. The post-doc grant will facilitate his return from Copenhagen to the University of Helsinki next winter. Without grants like this, many researchers might be tempted to stay abroad.

“The grant from the Instrumentarium Science Foundation makes it possible for me to continue my research after returning to Finland, and start my own line of research here. Post-doc grants are important for Finland’s international success, helping to bring excellence acquired from around the world back home,” Rosenholm reminds.

Modern state-of-the-art technology and the use of such technology come at a cost, so the grant funds are welcome indeed.

“In my own research, I use PET (Positron Emission Tomography), which is an isotope-based imaging technique. It provides accurate information about the functioning and metabolism of the body using short-lived radioactive tracers. However, both the equipment and the radioactive tracers are quite expensive."

Text: Kai Tarkka / Viestintäpalvelu Taika Oy
Picture: Marko Rosenholm