| Grant number: | 23/01211-7 |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| Start date: | June 01, 2023 |
| End date: | March 31, 2027 |
| Field of knowledge: | Biological Sciences - Biochemistry - Chemistry of Macromolecules |
| Principal Investigator: | Daniel Martins-de-Souza |
| Grantee: | Danyelle Silva Amaral |
| Host Institution: | Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
| Associated research grant: | 17/25588-1 - From the basic understanding to clinical biomarkers to schizophrenia: a neuroproteomics-centered multidisciplinary study, AP.TEM |
| Associated scholarship(s): | 24/22132-0 - Cannabidiol effects on energy metabolism and autophagy in astrocytes derived from embryonic stem cells, BE.EP.DR |
Abstract Schizophrenia is an incurable psychiatric disorder that affects approximately 24 million people worldwide. Antipsychotics are the first line of treatment to control symptoms, but these are not completely effective for the entire symptomatology of the disorder and can promote several side effects. It is known that cellular processes such as inflammation, glucose metabolism, mitochondrial function and response to reactive oxygen species (ROS) are altered in schizophrenia. It is also known that autophagic dysfunctions can occur in such a context, having mTOR pathway activation as one of the means. Thus, the modulation of autophagy through mTOR pathway activation has been postulated as a possible therapeutic target for mental disorders. Antagonists of the N-methyl-D-aspartate glutamate receptor, such as dizocilpine (MK-801), used to model schizophrenia, reproduce the hypofunction of the glutamatergic system, as observed in this disorder, in addition to alterations in the expression of glycolytic enzymes. However, autophagy remains a mechanism unexplored in this context. Furthermore, while studies suggest that cannabinoid compounds may play a protective role, the autophagic regulatory pathway mediated by these compounds is yet to be understood. Based on these facts, the general objective of this project is to investigate the relationship of cannabidiol (CBD) with the mTOR-mediated autophagic pathway and its possible neuro/glioprotective changes in astrocytes in vitro. For that, astrocytes derived from neural stem cells (NSCs) will be treated with MK-801 and CBD. Observing a protective role of CBD to evaluate the possible treatments involved, astrocytes will still be treated with AM251, AM630, WAY100635 and capsazepine to evaluate the possible treatments. Such cells will be evaluated using fluorescence microscopy, molecular biology techniques, such as Western Blotting, real-time PCR, proteomics and high-resolution respirometry (Seahorse), as well as the mutual changes in the autophagic process and glucose metabolism modulated by CBD. Thus, since the maintenance of autophagy can play a crucial role in neuro/glioprotection in schizophrenia pathobiology, we believe we can contribute to a better understanding of the role of CBD in autophagic modulation and thus contribute to a greater understanding of the neurobiology of this disorder and potential development of new therapies. | |
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