Evaluation of the molecular mechanisms of cannabigerol in inflammation and oxidative stress induced by LPS in human microglia in vitro.

• Grant number: 24/04243-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Anna Luiza Graf Rocha
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Neurodegenerative diseases (NDs) are characterized by neuronal loss and may be accompanied by protein abnormalities. These diseases do not yet have efficient treatments and tend to increase with population aging, making them important targets for study. Microglia are essential for maintaining homeostasis in the central nervous system (CNS), as well as actively participating in various physiological processes, such as immune signaling and redox balance control. Activated microglia stop secreting neurotrophic and neuroprotective factors and start expressing an inflammatory and neurotoxic character, correlating with neuroinflammatory processes present in various NDs. Environments with an increase in inflammatory mediators can lead to an increase in free radicals, in turn generating oxidative stress, and vice versa. This demonstrates the correlation between both states, which in turn are linked to various ND pathophysiologies. Thus, in order to understand NDs, it is necessary to use models of inflammation and oxidative stress in the CNS, and the challenge with a lipopolysaccharide (LPS) is widely used in vitro and in vivo. This endotoxin generates an acute inflammatory response and glial activation. On the other hand, compounds with anti-inflammatory and antioxidant properties are being studied as possible treatments for NDs. Cannabigerol (CBG), a non-psychotomimetic phytocannabinoid, has been studied for its potential neuroprotective effect by interacting with the endocannabinoid system. Studies have shown its anti-inflammatory and anti-nitrosative action in microglia; however, the biochemical changes involved in this response have not yet been elucidated. Thus, the aim of this project is to analyze changes in the expression of proteins and metabolites involved in the anti-inflammatory and anti-oxidant effect associated with CBG treatment in human microglia in vitro challenged with LPS. To understand the interactions between LPS and CBG, cultured human microglia will be evaluated using techniques such as fluorescence microscopy, proteomics and metabolomics. As the maintenance of these processes may play a crucial role in the effects induced by LPS, we believe that this research can contribute to a better understanding of the changes in the expression of proteins and metabolites involved in the anti-inflammatory and anti-oxidant effects of CBG treatment in microglia. Therefore, seeking to elucidate the pathways and mechanisms of action involved in the anti-inflammatory and anti-oxidative role of CBG in the context of NDs, providing specific proteins and pathway targets for future studies.