The impact of the anticonvulsant carbamazepine on brain function and cortisol stress axis activity during zebrafish development

• Grant number: 24/21537-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: March 30, 2025
• End date: March 29, 2026
• Field of knowledge: Biological Sciences - Physiology - Compared Physiology
• Principal Investigator: Renata Guimarães Moreira Whitton
• Grantee: Carlos Eduardo Delfino Vieira
• Supervisor: Mathilakath Vijayan
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Calgary, Canada
• Associated to the scholarship: 23/09837-2 - Pharmaceuticals as endocrine disruptors in Neotropical teleosts: an integrative approach, BP.PD

Abstract

The increase in the consumption of pharmaceutical products has resulted in an increase in the load in the environment. Carbamazepine (CBZ) is the most commonly used drug in epilepsy treatment, and its metabolites are commonly detected as persistent pharmaceuticals in the aquatic environment around the world. However, because it is a psychoactive drug, little attention has been paid to the toxicity of CBZ on the nervous system of fish, a non-target organism, and the underlying mechanisms are not well characterized. Previous studies have demonstrated that CBZ can affect the normal development of zebrafish embryos and the spontaneous movement of larvae by interfering with the GABA system and/or the Glu-GABA E/I balance, as well as increasing the extracellular concentration of the neurotransmitter serotonin (5-HT) in neuronal synapses in various fish species. The monoaminergic system is highly conserved in vertebrates, and the central and peripheral monoamines play an important role in modulating the cortisol stress activity. Consequently, disruptions of the monoaminergic pathway are a potential target for the effect of antidepressants on the cortisol stress axis function. Most studies have focused on the exposure of juveniles or adults to CBZ, often neglecting the impact associated with exposure during the critical windows of early development, which are highly sensitive to the impact of the contaminant, leading to changes in developmental programming. Thus, the objective of this project will be to test whether the zygotic deposition of environmentally relevant concentrations of the CBZ (10 and 100 ng), mimicking maternal transfer, will perturb early developmental 5HT in the brain, and to determine if CBZ can disrupt the ontogeny of the cortisol response and the functioning of the cortisol stress axis (HPI) in zebrafish.