Pharmacological and molecular mechanisms of a fluorescent nanoprobe containing cannabidiol in neurodevelopmental disorders models: implication for autism spectrum disorder and schizophrenia.

• Grant number: 23/11032-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2024
• End date: March 31, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Alline Cristina de Campos
• Grantee: Pedro Henrique Cassaro Lirio
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders, AP.TEM

Abstract

Current hypotheses relate neurodevelopmental disorders to alterations in neuroplastic processes in the development and structuring of neural circuitry. Additionally, genetic factors and variations in the timing of exposure to inflammatory environments during the pre- and postnatal periods may explain the differences between disorders. Among the known neurodevelopmental disorders, Autism Spectrum Disorder (ASD) and Schizophrenia stand out as particularly important for the present study. Due to the heterogeneity of phenotypes, pharmacological treatment of these disorders remain a significant challenge to this day. In this context, Cannabidiol (CBD), the main non-psychotomimetic phytocannabinoid found in Cannabis sativa, shows promise in the treatment of such disorders as it exhibits antipsychotic effects while also promoting neuroplastic processes. Data from our group indicate that a concentration of 0.06 µM of CBD during 3 days of exposure alters aggression profiles in Zebrafish larvae subjected to an ASD model, although it did not affect the endocannabinoid system signaling. On the other hand, to date, there have been no reports on the use of CBD as a treatment in Zebrafish models of schizophrenia. In the present study, we propose the use of fluorescent nanoencapsulated Cannabidiol (CBD-NP) in ASD and schizophrenia models, which, due to their liposolubility, can easily penetrate the central nervous system, serving as an effective pharmacological delivery system. Furthermore, they allow visualization of the distribution and localization of CBD-NP. Thus, the objective of this study is to investigate the similarities and differences in the mechanism of action of CBD in different neurodevelopmental disorder models. The following will be investigated: 1) Whether nanoencapsulated Cannabidiol is a better delivery and treatment strategy for CBD to the central nervous system; 2) The similarities and differences in behavioral alterations between the models treated with CBD-NP; 3) Whether the models and/or CBD-NP can alter the genome of 7dpf and 14dpf Zebrafish larvae; 4) The distribution pattern of CBD-NP in the central nervous system of Zebrafish larvae; 5) Whether the presented models and the treatment with CBD-NP can alter the endocannabinoid tone.