Neurochemical mechanisms involved in harmine-induced neuroprotection in cocaine-exposed SH-SY5Y cells.

• Grant number: 23/11078-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2024
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Tania Marcourakis
• Grantee: Juliana Lígia Freires Ribeiro
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Ayahuasca is a psychoactive drink commonly used by people from the Amazon region, its main active principles being N,N-dimethyltryptamine and beta-carbolines, harmine, harmaline, and tetrahydroharmine. Several studies explore the potential therapeutic use of psychedelic substances for treating mental disorders such as substance use. However, most of these studies focus on ethanol and tobacco use disorder, while studies for cocaine are limited, and there is no available drug treatment. This project aims to evaluate the potential neuroprotective effect of harmine against cocaine-induced toxicity in SH-SY5Y human neuroblastoma cells. In this way, it will be verified (i) the oxidative stress caused by cocaine and its metabolites and by the excess of dopamine; (ii) the increased expression of proteins related to neurogenesis and synaptogenesis (DCX, SNAP-25, synaptophysin, and PSD-25); (iii) increased concentration of mature brain-derived neurotrophic factor (mBDNF) and modulation of its pathway involved in neuroplasticity (Akt/mTOR, p70S6k and ERK1/2); (iv) and morphological aspects of neuroplasticity, such as neurite development, using CellProfiler software. Cocaine use harms health, promoting the development of mental disorders, and its excessive use has been reported by many countries, especially in South America. Therefore, studies involving harmine and other psychedelic substances are of great relevance in the search for treatments for cocaine use disorder.