Possible effects of paclitaxel on affective behavior, microglial activation and integrity of the blood-brain barrier in mice and the potential neuroprotective effect of cannabidiol

• Grant number: 24/22695-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Sabrina Francesca de Souza Lisboa
• Grantee: Audrey Beatriz Watanabe do Valle Queiroz
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Chemotherapy has revolutionized the treatment of various types of cancer; however, it can induce neurotoxicity in a significant proportion of patients, often culminating in cognitive impairment, commonly referred to as "chemobrain". Recently, emotional dysfunction has also been associated with chemobrain. Paclitaxel (PTX), used mainly in the treatment of breast cancer, is associated with neuroinflammation and increased permeability of the blood-brain barrier (BBB), leading to the neurotoxicity mentioned above. This scenario is worrying, given the increase in the number of cancer survivors with long-term cognitive sequelae. With this in mind, this study aims to investigate the behavioral changes in animals and the biochemical and structural changes in the brain induced by PTX, as well as the neuroprotective potential of cannabidiol (CBD), a non-psychotropic compound from Cannabis sativa. CBD has already demonstrated anti-inflammatory and antioxidant properties, as well as favoring neurogenesis and the integrity of the BBB. Using cell and molecular biology techniques and behavioral assays, we will investigate whether CBD can attenuate the neurotoxic effects of paclitaxel, focusing on affective behavior, BBB integrity and neuroinflammation. The results of this study may open up new therapeutic possibilities for minimizing the neurological complications associated with chemotherapy, to improve patients quality of life.