Exploring Canabidiol mechanisms of action on mouse nervous system using different omic strategies

• Grant number: 23/18022-2
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2024
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Andre Schwambach Vieira
• Grantee: Andre Schwambach Vieira
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Laís Rosa Viana ; Maria Carolina Pedro Athié

Abstract

Cannabidiol (CBD) is the second most abundant phytocannabinoid found in the resin produced by the female flowers of the Cannabis sativa plant. The use of CBD has emerged as a potential therapeutic strategy capable of inducing neuroprotective, anticonvulsive, antiepileptic, anxiolytic, and antipsychotic effects in both animal models and humans. However, there remains a need for further studies to explore the effects of CBD administration on the molecular machinery of the nervous system, as well as to investigate the specific mechanisms through which CBD exerts its therapeutic effects. A previous study by our research group demonstrated that the administration of 100mg/kg of CBD for 7 days induced a reduction in the expression level of genes involved in mitochondrial electron transport chain and ribosomal biogenesis, and an increase in the expression level of genes related to chromatin modifications and synaptic organization in the CA1 region of the hippocampus. These findings may indicate the mechanism of action of CBD in the hippocampus, however, they do not yet explore which mechanisms are induced by different dosages of this molecule and whether the same mechanisms can be observed in other regions of the nervous system. Given that alterations in the function of the prefrontal cortex are associated with neuropsychiatric conditions such as schizophrenia, depression, and substance dependence, understanding the potential effects of CBD, at different dosages, in this region is critical for a better understanding of the mechanisms responsible for the therapeutic effects of this molecule. Furthermore, with the aim of deepening the understanding of the potential effects of CBD, we will also employ metabolomic analysis of different structures of the nervous system in mice treated with this molecule. Therefore, the present study aims to evaluate the alterations in the gene expression profile induced by the administration of CBD at different doses in various structures of the medial prefrontal cortex of mice, as well as the CA1 and CA3 regions of the hippocampus. We will also perform metabolome analysis through magnetic resonance spectroscopy of these regions of the nervous system after different doses of CBD, so that through a multi-omic analysis strategy, a deeper understanding of the effects of CBD in regions of the nervous system critically involved in conditions such as epilepsy and disorders of systems involved in executive and emotional functions can be achieved. (AU)