Cannabidiol effects on energy metabolism and autophagy in astrocytes derived from embryonic stem cells

• Grant number: 24/22132-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Danyelle Silva Amaral
• Supervisor: Sovan Sarkar
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Birmingham, England
• Associated to the scholarship: 23/01211-7 - Cannabidiol effects on glucose metabolism and autophagy in astrocytes in the context of schizophrenia, BP.DR

Abstract

Psychiatric disorders like schizophrenia and depression have common underlying mechanisms including glutamatergic dysfunction, neuroinflammation, mitochondrial dysfunction, and their crosstalk. Impairment in autophagy, a cell survival process essential for cellular, energy and metabolic homeostasis, has been linked to these alterations. A promising drug candidate for psychiatric disorders is cannabidiol (CBD) that has been shown to modulate autophagy, but its neuroprotective mechanisms are not fully understood. This project aims to investigate the mechanisms related to the neuroprotective functions of CBD, involving autophagy and energy metabolism, against glutamatergic hypofunction and inflammatory stimuli in human embryonic stem cell (hESC)-derived astrocytes. To study the role of autophagy in executing the neuroprotective effects of CBD, a genetic hESC model of autophagy deficiency will be utilized for generating human astrocytes with loss of autophagy. The study will involve analyses of autophagy and endocannabinoid system, along with disease-relevant phenotypes resulting from defective autophagy including aggresome formation, mitochondrial dysfunction, and cell death, coupled with mitochondrial proteomics and cellular metabolomics. This work will provide a deeper understanding of the beneficial effects of CBD via the interplay between autophagy, energy metabolism, and neuroprotection for developing a novel therapeutic strategy for psychiatric disorders.