From molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Digital do Instituto Evandro Chagas (Patuá) |
Texto Completo: | https://patua.iec.gov.br/handle/iec/4517 |
Resumo: | 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. |
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Bittencourt, Leonardo OliveiraChemelo, Victória SantosAragão, Walessa Alana BragançaPuty, BrunaDionizio, AlineTeixeira, Francisco BrunoFernandes, Mileni SilvaSilva, Márcia Cristina FreitasFernandes, Luanna Melo PereiraOliveira, Edivaldo Herculano Corrêa deBuzalaf, Marilia Afonso RabeloLopez, Maria Elena CrespoMaia, Cristiane do Socorro FerrazLima, Rafael Rodrigues2022-05-25T18:41:54Z2022-05-25T18:41:54Z2022BITTENCOURT, Leonardo Oliveira 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, v. 23, n. 1, p. 1-17, Dec. 2022.1422-0067https://patua.iec.gov.br/handle/iec/451710.3390/ijms23010111Abstract: 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.CNPq—Brazilian Ministry of Science, Technology and Innovation scholarships. Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, from Brazilian Ministry of Education (finance code 001). Pró-reitoria de Pesquisa e Pós-graduação (PROPESP) from Federal University of Pará (UFPA).Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, BrazilFederal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil IdiomaFederal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, BrazilFederal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, BrazilUniversity of São Paulo. Department of Biological Sciences. Bauru Dental School. Bauru, SP, BrazilFederal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, BrazilUniversity of São Paulo. Department of Biological Sciences. Bauru Dental School. Bauru, SP, BrazilFederal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, BrazilFederal University of Pará. Institute of Health Sciences. Laboratory Pharmacology of Inflammation and Behavior. Belém, PA, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Citogenética. Ananindeua, PA, BrasilUniversity of São Paulo. Department of Biological Sciences. Bauru Dental School. Bauru, SP, BrazilFederal University of Pará. Institute of Biological Sciences. Laboratory of Molecular Pharmacology. Belém, PA, BrazilFederal University of Pará. Institute of Health Sciences. Laboratory Pharmacology of Inflammation and Behavior. Belém, PA, BrazilFederal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, BrazilengMDPIFrom molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleMercúrio / toxicidadeIntoxicação do Sistema Nervoso por MercúrioProteômicaDestreza Motorainfo:eu-repo/semantics/openAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALFrom molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats.pdfFrom molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats.pdfapplication/pdf3781510https://patua.iec.gov.br/bitstreams/25b78cd9-42db-4556-b487-0fff5d2ba9f7/download290019b67288e531384f024e83794020MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82182https://patua.iec.gov.br/bitstreams/c0b4a588-dfdc-4f48-b508-ae5ebcebdc32/download11832eea31b16df8613079d742d61793MD52TEXTFrom molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats.pdf.txtFrom molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats.pdf.txtExtracted texttext/plain81859https://patua.iec.gov.br/bitstreams/5baf8a89-c59d-494c-8b0e-72c4f56f6cc7/download6a1425c5c37d5bf49367e8fabcaa717cMD55THUMBNAILFrom molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats.pdf.jpgFrom molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats.pdf.jpgGenerated Thumbnailimage/jpeg5759https://patua.iec.gov.br/bitstreams/2aa8879e-9b56-4ee9-8e6d-2bcf1a07ded3/downloadbced1cf854d51a759326662f14b7b189MD56iec/45172022-10-21 00:26:02.467oai:patua.iec.gov.br:iec/4517https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-21T00:26:02Repositório Digital do Instituto Evandro Chagas (Patuá) - 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dc.title.pt_BR.fl_str_mv |
From molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats |
title |
From molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats |
spellingShingle |
From molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats Bittencourt, Leonardo Oliveira Mercúrio / toxicidade Intoxicação do Sistema Nervoso por Mercúrio Proteômica Destreza Motora |
title_short |
From molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats |
title_full |
From molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats |
title_fullStr |
From molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats |
title_full_unstemmed |
From molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats |
title_sort |
From molecules to behavior in long-term inorganic mercury intoxication: unraveling proteomic features in cerebellar neurodegeneration of rats |
author |
Bittencourt, Leonardo Oliveira |
author_facet |
Bittencourt, Leonardo Oliveira Chemelo, Victória Santos Aragão, Walessa Alana Bragança Puty, Bruna Dionizio, Aline Teixeira, Francisco Bruno Fernandes, Mileni Silva Silva, Márcia Cristina Freitas Fernandes, Luanna Melo Pereira Oliveira, Edivaldo Herculano Corrêa de Buzalaf, Marilia Afonso Rabelo Lopez, Maria Elena Crespo Maia, Cristiane do Socorro Ferraz Lima, Rafael Rodrigues |
author_role |
author |
author2 |
Chemelo, Victória Santos Aragão, Walessa Alana Bragança Puty, Bruna Dionizio, Aline Teixeira, Francisco Bruno Fernandes, Mileni Silva Silva, Márcia Cristina Freitas Fernandes, Luanna Melo Pereira Oliveira, Edivaldo Herculano Corrêa de Buzalaf, Marilia Afonso Rabelo Lopez, Maria Elena Crespo Maia, Cristiane do Socorro Ferraz Lima, Rafael Rodrigues |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Bittencourt, Leonardo Oliveira Chemelo, Victória Santos Aragão, Walessa Alana Bragança Puty, Bruna Dionizio, Aline Teixeira, Francisco Bruno Fernandes, Mileni Silva Silva, Márcia Cristina Freitas Fernandes, Luanna Melo Pereira Oliveira, Edivaldo Herculano Corrêa de Buzalaf, Marilia Afonso Rabelo Lopez, Maria Elena Crespo Maia, Cristiane do Socorro Ferraz Lima, Rafael Rodrigues |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
Mercúrio / toxicidade Intoxicação do Sistema Nervoso por Mercúrio Proteômica Destreza Motora |
topic |
Mercúrio / toxicidade Intoxicação do Sistema Nervoso por Mercúrio Proteômica Destreza Motora |
description |
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. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-05-25T18:41:54Z |
dc.date.available.fl_str_mv |
2022-05-25T18:41:54Z |
dc.date.issued.fl_str_mv |
2022 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
BITTENCOURT, Leonardo Oliveira 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, v. 23, n. 1, p. 1-17, Dec. 2022. |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/4517 |
dc.identifier.issn.-.fl_str_mv |
1422-0067 |
dc.identifier.doi.pt_BR.fl_str_mv |
10.3390/ijms23010111 |
identifier_str_mv |
BITTENCOURT, Leonardo Oliveira 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, v. 23, n. 1, p. 1-17, Dec. 2022. 1422-0067 10.3390/ijms23010111 |
url |
https://patua.iec.gov.br/handle/iec/4517 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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MDPI |
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MDPI |
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