Understanding ayahuasca effects in major depressive disorder treatment through invitro metabolomics and bioinformatics

Author(s)

Zandonadi, Flavia S. ; Silva, Alex Ap. Rosini ; Melo, Aline A. S. ; Ignarro, Raffaela S. ; Matos, Taynara S. ; Santos, Emerson A. F. ; Barbosa, Luidy D. ; Oliveira, Alexandre L. R. ; Porcari, Andreia M. ; Sussulini, Alessandra

• Document type: Journal article
• Source: ANALYTICAL AND BIOANALYTICAL CHEMISTRY; v. N/A, p. 18-pg., 2023-01-30.

Abstract

Emerging insights from metabolomic-based studies of major depression disorder (MDD) are mainly related to biochemical processes such as energy or oxidative stress, in addition to neurotransmission linked to specific metabolite intermediates. Hub metabolites represent nodes in the biochemical network playing a critical role in integrating the information flow in cells between metabolism and signaling pathways. Limited technical-scientific studies have been conducted to understand the effects of ayahuasca (Aya) administration in the metabolism considering MDD molecular context. Therefore, this work aims to investigate an in vitro primary astrocyte model by untargeted metabolomics of two cellular subfractions: secretome and intracellular content after pre-defined Aya treatments, based on DMT concentration. Mass spectrometry (MS)-based metabolomics data revealed significant hub metabolites, which were used to predict biochemical pathway alterations. Branched-chain amino acid (BCAA) metabolism, and vitamin B6 and B3 metabolism were associated to Aya treatment, as "housekeeping " pathways. Dopamine synthesis was overrepresented in the network results when considering the lowest tested DMT concentration (1 mu mol L-1). Building reaction networks containing significant and differential metabolites, such as nicotinamide, L-DOPA, and L-leucine, is a useful approach to guide on dose decision and pathway selection in further analytical and molecular studies. (AU)

• FAPESP's process: 18/01525-3 - Metabolomic studies of depression patients treated with ayahuasca
• Grantee: Alessandra Sussulini
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50867-3 - INCT 2014: National Institute of Science and Technology in Bioanalysis
• Grantee: Marco Aurelio Zezzi Arruda
• Support Opportunities: Research Projects - Thematic Grants