In vivo and in silico studies to identify mechanisms Associated with nurr1 modulation following early Life exposure to permethrin in rats

Detalhes bibliográficos
Autor(a) principal: Fedeli, Donatella
Data de Publicação: 2017
Outros Autores: Montani, Maura, Bordoni, Laura, Galeazzi, Roberta, Nasuti, Cinzia, Correia-sá, Luísa, Domingues, Valentina F., Jayant, Maini, Brahmachari, Vani, Massaccesi, Luca, Laudadio, Emiliano, Gabbianelli, Rosita
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.22/9495
Resumo: The present work was designed to study the mechanisms associated with Nurr1 modulation following early life permethrin (PERM) treatment during rat’s life span. Here we demonstrate that PERM exposure in rats, at a dose close to No Observed Adverse Effect Level (NOAEL) for 15 days during neonatal brain development leads to its accumulation long after exposure. In striatum from adolescent rats we detected an increase in DNA methyltransferases (DNMTs) such as DNMT1, DNMT3a, Tyrosine hydroxylase, monomeric and aggregated α-synuclein protein levels. Adult rats showed enhanced DNMT3b and α-synuclein aggregation compared to the control group, while with aging a significant decrease in all biomarkers studied was observed. No changes in Nurr1 promoter methylation in adolescent, adult and old rats were found. In silico studies showed clear evidence of a strong binding interaction between PERM and its metabolite 3-phenoxybenzoic acid with the nuclear orphan receptor Nurr1. These findings suggest that an additional interference with the dopaminergic neuron pathway could occur in situ during PERM accumulation in brain. Therefore, Nurr1 modulation in early life PERM-treated rats, depends on age-related adaptive responses in animals.
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spelling In vivo and in silico studies to identify mechanisms Associated with nurr1 modulation following early Life exposure to permethrin in ratsEarly life permethrin exposureNurr1 promoter methylationDNMTsa-synucleinMolecular dockingRatThe present work was designed to study the mechanisms associated with Nurr1 modulation following early life permethrin (PERM) treatment during rat’s life span. Here we demonstrate that PERM exposure in rats, at a dose close to No Observed Adverse Effect Level (NOAEL) for 15 days during neonatal brain development leads to its accumulation long after exposure. In striatum from adolescent rats we detected an increase in DNA methyltransferases (DNMTs) such as DNMT1, DNMT3a, Tyrosine hydroxylase, monomeric and aggregated α-synuclein protein levels. Adult rats showed enhanced DNMT3b and α-synuclein aggregation compared to the control group, while with aging a significant decrease in all biomarkers studied was observed. No changes in Nurr1 promoter methylation in adolescent, adult and old rats were found. In silico studies showed clear evidence of a strong binding interaction between PERM and its metabolite 3-phenoxybenzoic acid with the nuclear orphan receptor Nurr1. These findings suggest that an additional interference with the dopaminergic neuron pathway could occur in situ during PERM accumulation in brain. Therefore, Nurr1 modulation in early life PERM-treated rats, depends on age-related adaptive responses in animals.ElsevierRepositório Científico do Instituto Politécnico do PortoFedeli, DonatellaMontani, MauraBordoni, LauraGaleazzi, RobertaNasuti, CinziaCorreia-sá, LuísaDomingues, Valentina F.Jayant, MainiBrahmachari, VaniMassaccesi, LucaLaudadio, EmilianoGabbianelli, Rosita20172117-01-01T00:00:00Z2017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.22/9495eng10.1016/j.neuroscience.2016.10.071metadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-13T12:50:53Zoai:recipp.ipp.pt:10400.22/9495Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:30:04.995730Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv In vivo and in silico studies to identify mechanisms Associated with nurr1 modulation following early Life exposure to permethrin in rats
title In vivo and in silico studies to identify mechanisms Associated with nurr1 modulation following early Life exposure to permethrin in rats
spellingShingle In vivo and in silico studies to identify mechanisms Associated with nurr1 modulation following early Life exposure to permethrin in rats
Fedeli, Donatella
Early life permethrin exposure
Nurr1 promoter methylation
DNMTs
a-synuclein
Molecular docking
Rat
title_short In vivo and in silico studies to identify mechanisms Associated with nurr1 modulation following early Life exposure to permethrin in rats
title_full In vivo and in silico studies to identify mechanisms Associated with nurr1 modulation following early Life exposure to permethrin in rats
title_fullStr In vivo and in silico studies to identify mechanisms Associated with nurr1 modulation following early Life exposure to permethrin in rats
title_full_unstemmed In vivo and in silico studies to identify mechanisms Associated with nurr1 modulation following early Life exposure to permethrin in rats
title_sort In vivo and in silico studies to identify mechanisms Associated with nurr1 modulation following early Life exposure to permethrin in rats
author Fedeli, Donatella
author_facet Fedeli, Donatella
Montani, Maura
Bordoni, Laura
Galeazzi, Roberta
Nasuti, Cinzia
Correia-sá, Luísa
Domingues, Valentina F.
Jayant, Maini
Brahmachari, Vani
Massaccesi, Luca
Laudadio, Emiliano
Gabbianelli, Rosita
author_role author
author2 Montani, Maura
Bordoni, Laura
Galeazzi, Roberta
Nasuti, Cinzia
Correia-sá, Luísa
Domingues, Valentina F.
Jayant, Maini
Brahmachari, Vani
Massaccesi, Luca
Laudadio, Emiliano
Gabbianelli, Rosita
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Politécnico do Porto
dc.contributor.author.fl_str_mv Fedeli, Donatella
Montani, Maura
Bordoni, Laura
Galeazzi, Roberta
Nasuti, Cinzia
Correia-sá, Luísa
Domingues, Valentina F.
Jayant, Maini
Brahmachari, Vani
Massaccesi, Luca
Laudadio, Emiliano
Gabbianelli, Rosita
dc.subject.por.fl_str_mv Early life permethrin exposure
Nurr1 promoter methylation
DNMTs
a-synuclein
Molecular docking
Rat
topic Early life permethrin exposure
Nurr1 promoter methylation
DNMTs
a-synuclein
Molecular docking
Rat
description The present work was designed to study the mechanisms associated with Nurr1 modulation following early life permethrin (PERM) treatment during rat’s life span. Here we demonstrate that PERM exposure in rats, at a dose close to No Observed Adverse Effect Level (NOAEL) for 15 days during neonatal brain development leads to its accumulation long after exposure. In striatum from adolescent rats we detected an increase in DNA methyltransferases (DNMTs) such as DNMT1, DNMT3a, Tyrosine hydroxylase, monomeric and aggregated α-synuclein protein levels. Adult rats showed enhanced DNMT3b and α-synuclein aggregation compared to the control group, while with aging a significant decrease in all biomarkers studied was observed. No changes in Nurr1 promoter methylation in adolescent, adult and old rats were found. In silico studies showed clear evidence of a strong binding interaction between PERM and its metabolite 3-phenoxybenzoic acid with the nuclear orphan receptor Nurr1. These findings suggest that an additional interference with the dopaminergic neuron pathway could occur in situ during PERM accumulation in brain. Therefore, Nurr1 modulation in early life PERM-treated rats, depends on age-related adaptive responses in animals.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-01-01T00:00:00Z
2117-01-01T00:00:00Z
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.uri.fl_str_mv http://hdl.handle.net/10400.22/9495
url http://hdl.handle.net/10400.22/9495
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1016/j.neuroscience.2016.10.071
dc.rights.driver.fl_str_mv metadata only access
info:eu-repo/semantics/openAccess
rights_invalid_str_mv metadata only access
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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