Deciphering the Global Proteomic Profile Involved in Methylmercury-Induced Cerebellar Neurodegeneration and Motor Dysfunction in Adult Rats

Leonardo Oliveira Bittencourt, Pedro Philipe Moreira Matta, Priscila Cunha Nascimento, Luciana Eiró-Quirino, Walessa Alana Bragança Aragão, Aline Dionizio, Luanna Melo Pereira Fernandes, Márcia Cristina Freitas Silva, Marília Afonso Rabelo Buzalaf, Michael Aschner, Maria Elena Crespo-Lopez, Cristiane Socorro Ferraz Maia, Rafael Rodrigues Lima

Research output: Contribution to journalArticlepeer-review

Abstract

Mercury is a ubiquitous pollutant in the environment with potential neurotoxic effects. Several populations are susceptible to mercurial exposure, especially methylmercury (MeHg) at low doses for long periods through food consumption. Given this, the present work aimed to assess the effects of long-term MeHg exposure on the cerebellum of rats from a translational perspective using a representative dose, assessing molecular, biochemical, morphological, and behavioral parameters. The model was produced by administering 40 µg/kg of MeHg for 60 days to adult male Wistar rats by oral gavage. As a result of this exposure, the animals presented motor deficits in open field and rotarod tests which were associated with an increase in total mercury content in cerebellar parenchyma, a reduction in antioxidant competence against peroxyl radicals, and increased nitrite and lipid peroxidation levels. The proteomic approach showed 317 modulated proteins. Such findings were associated with reductions in mature neuron and Purkinje cell densities and glial fibrillary acidic protein immunostained areas and increased microglial density. In addition, decreases in myelin basic protein and synaptophysin immunostaining were also observed. The results thus provided new evidence of the mechanisms underlying complex MeHg-induced neurodegeneration, especially the proteins underlying the biochemical and morphological features associated with motor dysfunction.

Original languageEnglish (US)
Article number531
JournalToxics
Volume10
Issue number9
DOIs
StatePublished - Sep 2022

Keywords

  • microglia
  • neurodegeneration
  • neurotoxicology
  • organic mercury
  • oxidative stress
  • proteomic

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Chemical Health and Safety

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