Characterization of Behavioral and Plasticity Effects of Adolescent Cannabidiol Treatment in a Mouse Model of SATB2-Associated Syndrome

• Grant number: 25/23908-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: March 03, 2026
• End date: March 02, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Alline Cristina de Campos
• Grantee: Pedro Henrique Cassaro Lirio
• Supervisor: Ismael Galve Roperh
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Universidad Complutense de Madrid (UCM), Spain
• Associated to the scholarship: 23/11032-2 - Pharmacological and molecular mechanisms of a fluorescent nanoprobe containing cannabidiol in neurodevelopmental disorders models: implication for autism spectrum disorder and schizophrenia., BP.DR

Abstract

SATB2-associated syndrome (SAS), or Glass syndrome, is a rare genetic disorder caused by mutations in the SATB2 gene, leading to intellectual disability, autism spectrum disorder (ASD)-related behaviors, and an increased risk of epilepsy. Given the overlap between SAS and other neurodevelopmental disorders, cannabidiol (CBD), a non-psychotomimetic compound derived from Cannabis sativa, has emerged as a promising therapeutic candidate due to its known antipsychotic and anxiolytic effects. Recent evidence suggests that CBD may act as a negative allosteric modulator of cannabinoid receptor 1 (CB1), a mechanism that could reverse behavioral and neuroplasticity deficits associated with neurodevelopmental disorders. This project aims to investigate whether CBD, delivered through a nanoencapsulation approach (nanoCBD), as well as CB1 receptor antagonism can reverse behavioral deficits in a mouse model of SAS. Specifically, the study will evaluate the effects of CBD and CB1 receptor modulation on motor activity, memory, and social behaviors in male and female SATB2 knockout mice. Additionally, we will explore how these treatments influence cortical development and glial cell activity in key brain regions associated with those behaviors such as the prefrontal cortex and hippocampus. Altogether, using behavioral assays, and gene expression studies, this project will explore the molecular and functional effects of CB1 modulation during adolescence, a critical period of neurodevelopment. This project represents an important step in elucidating the therapeutic potential of cannabinoids in treating SAS, providing new insights into the role of the endocannabinoid system in neurodevelopmental disorders. (AU)