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Article

From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats

by
Leonardo Oliveira Bittencourt
1,†,
Victória Santos Chemelo
1,†,
Walessa Alana Bragança Aragão
1,
Bruna Puty
1,
Aline Dionizio
2,
Francisco Bruno Teixeira
1,
Mileni Silva Fernandes
2,
Márcia Cristina Freitas Silva
1,
Luanna Melo Pereira Fernandes
3,
Edivaldo Herculano Corrêa de Oliveira
4,
Marilia Afonso Rabelo Buzalaf
2,
Maria Elena Crespo-Lopez
5,
Cristiane do Socorro Ferraz Maia
3 and
Rafael Rodrigues Lima
1,*
1
Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil
2
Department of Biological Sciences, Bauru Dental School, University of São Paulo, Bauru 17012-901, SP, Brazil
3
Laboratory Pharmacology of Inflammation and Behavior, Institute of Health Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil
4
Laboratory of Cytogenetics, Environmental Session, Evandro Chagas Institute, Ananindeua 66093-020, PA, Brazil
5
Laboratory of Molecular Pharmacology, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2022, 23(1), 111; https://doi.org/10.3390/ijms23010111
Submission received: 24 October 2021 / Revised: 21 November 2021 / Accepted: 22 November 2021 / Published: 22 December 2021
(This article belongs to the Special Issue Neurodegenerative Diseases: From Molecular Basis to Therapy)
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Abstract

Mercury is a severe environmental pollutant with neurotoxic effects, especially when exposed for long periods. Although there are several evidences regarding mercury toxicity, little is known about inorganic mercury (IHg) species and cerebellum, one of the main targets of mercury associated with the neurological symptomatology of mercurial poisoning. Besides that, the global proteomic profile assessment is a valuable tool to screen possible biomarkers and elucidate molecular targets of mercury neurotoxicity; however, the literature is still scarce. Thus, this study aimed to investigate the effects of long-term exposure to IHg in adult rats’ cerebellum and explore the modulation of the cerebellar proteome associated with biochemical and functional outcomes, providing evidence, in a translational perspective, of new mercury toxicity targets and possible biomarkers. Fifty-four adult rats were exposed to 0.375 mg/kg of HgCl2 or distilled water for 45 days using intragastric gavage. Then, the motor functions were evaluated by rotarod and inclined plane. The cerebellum was collected to quantify mercury levels, to assess the antioxidant activity against peroxyl radicals (ACAPs), the lipid peroxidation (LPO), the proteomic profile, the cell death nature by cytotoxicity and apoptosis, and the Purkinje cells density. The IHg exposure increased mercury levels in the cerebellum, reducing ACAP and increasing LPO. The proteomic approach revealed a total 419 proteins with different statuses of regulation, associated with different biological processes, such as synaptic signaling, energy metabolism and nervous system development, e.g., all these molecular changes are associated with increased cytotoxicity and apoptosis, with a neurodegenerative pattern on Purkinje cells layer and poor motor coordination and balance. In conclusion, all these findings feature a neurodegenerative process triggered by IHg in the cerebellum that culminated into motor functions deficits, which are associated with several molecular features and may be related to the clinical outcomes of people exposed to the toxicant.
Keywords: mercury; central nervous system; proteomic; motor functions mercury; central nervous system; proteomic; motor functions

Share and Cite

MDPI and ACS Style

Bittencourt, L.O.; Chemelo, V.S.; Aragão, W.A.B.; Puty, B.; Dionizio, A.; Teixeira, F.B.; Fernandes, M.S.; Silva, M.C.F.; Fernandes, L.M.P.; de Oliveira, E.H.C.; et al. From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats. Int. J. Mol. Sci. 2022, 23, 111. https://doi.org/10.3390/ijms23010111

AMA Style

Bittencourt LO, Chemelo VS, Aragão WAB, Puty B, Dionizio A, Teixeira FB, Fernandes MS, Silva MCF, Fernandes LMP, de Oliveira EHC, et al. From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats. International Journal of Molecular Sciences. 2022; 23(1):111. https://doi.org/10.3390/ijms23010111

Chicago/Turabian Style

Bittencourt, Leonardo Oliveira, Victória Santos Chemelo, Walessa Alana Bragança Aragão, Bruna Puty, Aline Dionizio, Francisco Bruno Teixeira, Mileni Silva Fernandes, Márcia Cristina Freitas Silva, Luanna Melo Pereira Fernandes, Edivaldo Herculano Corrêa de Oliveira, and et al. 2022. "From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats" International Journal of Molecular Sciences 23, no. 1: 111. https://doi.org/10.3390/ijms23010111

APA Style

Bittencourt, L. O., Chemelo, V. S., Aragão, W. A. B., Puty, B., Dionizio, A., Teixeira, F. B., Fernandes, M. S., Silva, M. C. F., Fernandes, L. M. P., de Oliveira, E. H. C., Buzalaf, M. A. R., Crespo-Lopez, M. E., Maia, C. d. S. F., & Lima, R. R. (2022). From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats. International Journal of Molecular Sciences, 23(1), 111. https://doi.org/10.3390/ijms23010111

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