Sara Alves Xapell  is a Professor at the Institute of Pharmacology and Neurosciences of the Faculty of Medicine of the University of Lisbon and Researcher at the Ana Sebastião Lab, Institute of Molecular Medicine João Lobo Antunes.

She studies the plasticity of the brain, “this amazing organ that throughout life can continue to produce new neurons”.

Sara Xapelli, together with Professor Frederico Simões do Couto and Ph.D. student Rui Rodrigues, saw their project in the area of depression and study of neural stem cells and type 2 cannabinoid receptor, awarded with funding from the International Society for Neurochemistry. According to the Professor, "it is a grant to support independent career development". "It recognises the work done so far".

The news@FMUL spoke to her, who explained that the stimulation of type 2 cannabinoid receptors, present in neural stem cells, can result in antidepressant effects.

The Professor received a grant from the International Society for Neurochemistry, as a result of a project in the area of depression and the study of neural stem cells and the type 2 cannabinoid receptor. Can you tell us of this study consists of?

Sara Xapelli: This project, funded by the International Society for Neurochemistry (ISN), aims to support young researchers to establish themselves independently. It has a  curriculum assessment  component and a scientific project assessment.

In this sense, our work, funded by this project, aims to explore adult neural stem cells as a potential therapeutic platform to combat depression, exploring the role of type 2 cannabinoid receptors (CB2R) in these cells as a potential antidepressant strategy. Our hypothesis is that stimulation of CB2Rs present in neural stem cells results in significant antidepressant effects due to the formation of new neurons. To test this hypothesis, we used two different approaches in the project: fundamental science and a more translational approach. In the first, we use animal models for our study and in the second we will evaluate the levels of endocannabinoids in the blood of patients with depression to relate them to the preclinical data.

What is a type 2 cannabinoid receptor?

Sara Xapelli: Our organism has endogenous molecules, the endocannabinoids, which mainly activate two types of receptors, type 1 and type 2 cannabinoid receptors, and which participate in the regulation of the nervous system activity. These receptors are widely described as being involved in the regulation of various physiological processes. The type 2 receptor (CB2R) has an anti-inflammatory role. CB2Rs are also particularly relevant because their activation does not trigger undesirable effects, such as when type 1 receptors are activated, associated with most cannabinoids, like tetrahydrocannabinol (THC), which is responsible for the psychoactive properties of cannabis.

Could these receptors have any beneficial effect/applicability in terms of treatment or symptom control, in neurodegenerative diseases?

Sara Xapelli: Right now we are focused on depression, taking into account the data published in the literature and our preliminary data. However, its importance has been described in animal models with neurodegenerative diseases, such as Alzheimer's disease, given its anti-inflammatory role.

What will be the applicability of the funding in this project?

Sara Xapelli: This funding will help to develop our research work, opening doors to better diagnostic tools and possible future therapies. However, this type of studies requires high funding, so new sources will be needed.

In what sense was the duo with Professor Frederico Simões do Couto the recipe for attracting attention to the project?

Sara Xapelli: The last task of our project is to study the levels of endocannabinoids in patients with depression. Professor Frederico, being a psychiatrist with experience and interest in this topic, is a key element for the interconnection between fundamental and translational science. To be able to find biomarkers for this pathology would be of enormous importance.

On the other hand, I would like to point out that the starting point of this project was Rui Rodrigues, a Ph.D. student supervised by me and by Professor Carlos Fitzsimons (University of Amsterdam). Rui has been interested in the role of endocannabinoids in the formation of new neurons for some years and has been responsible for the conducting this research strand in our laboratory. 

What will the next steps be?

Sara Xapelli: The next steps will be to start clinical studies. 

Cristina Bastos

Editorial Team