Toxicogenomic cross-species studies to develop an adverse outcome pathway framework for understanding and predicting both neurotoxicity during development and manganese-induced neurodegeneration

• Grant number: 16/00371-7
• Support Opportunities: Scholarships abroad - Research
• Effective date (Start): September 01, 2016
• Effective date (End): March 31, 2017
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Raúl Bonne Hernández
• Grantee: Raúl Bonne Hernández
• Host Investigator: Ashkan Golshani
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Research place: Carleton University, Canada

Abstract

Manganese (Mn) is the twelfth most abundant element in the earth crust. Mn is an essential trace mineral in nutrition that can be (neuro)toxic, especially during developmental stages by unclear mechanisms that suggest additional and improved studies. In this way, adverse outcome pathways (AOPs) are novel tools designed to provide a clear-cut mechanistic representation of critical toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event (MIE), a series of intermediate steps and key events, and an adverse outcome (AO). These AO can be revealed by toxicogenomics approaches, which combines toxicology with genomics or other high throughput molecular profiling technologies such as transcriptomics, proteomics, metabolomics, and epigenomics. Recently, our group using toxicogenomics approaches in alternative animal model have discovered that Mn disrupt several pathways associated with cellular homeostasis, including metal dyshomoestasis, protein metabolism impairment, Alzheimer's disease, Huntington disease and Parkinson disease. Hence, in this project is being hypothetisized that if adverse outcome pathways induced by manganese species are conserved cross-species, this must improve the understanding of the unclear neuro(toxicological) mechanisms of this metal and its involving in neurodegeneration. This manner, the present project aims to discover if these pathways alterations are conserved among different models. The results of this project may improve the available tool for environmental and human risk assessment associated with the manganese. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HERNANDEZ, RAUL BONNE; CARRASCAL, MONTSERRAT; ABIAN, JOAQUIN; MICHALKE, BERNHARD; FARINA, MARCELO; GONZALEZ, YASMILDE RODRIGUEZ; IYIRHIARO, GRACE O.; MOTESHAREIE, HOUMAN; BURNSIDE, DANIEL; GOLSHANI, ASHKAN; et al. Manganese-induced neurotoxicity in cerebellar granule neurons due to perturbation of cell network pathways with potential implications for neurodegenerative disorders. METALLOMICS, v. 12, n. 11, p. 1656-1678, NOV 1 2020. (16/50483-6, 15/24207-9, 16/00371-7, 14/08990-2)

HERNANDEZ, RAUL BONNE; MOTESHAREIE, HOUMAN; BURNSIDE, DANIEL; MCKAY, BRUCE; GOLSHANI, ASHKAN. Manganese-induced cellular disturbance in the baker's yeast, Saccharomyces cerevisiae with putative implications in neuronal dysfunction. SCIENTIFIC REPORTS, v. 9, APR 25 2019. (16/00371-7, 16/50483-6)