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

dc.contributor.authorFedeli, Donatella
dc.contributor.authorMontani, Maura
dc.contributor.authorBordoni, Laura
dc.contributor.authorGaleazzi, Roberta
dc.contributor.authorNasuti, Cinzia
dc.contributor.authorCorreia-sá, Luísa
dc.contributor.authorDomingues, Valentina F.
dc.contributor.authorJayant, Maini
dc.contributor.authorBrahmachari, Vani
dc.contributor.authorMassaccesi, Luca
dc.contributor.authorLaudadio, Emiliano
dc.contributor.authorGabbianelli, Rosita
dc.date.accessioned2017-02-02T14:55:37Z
dc.date.embargo2117
dc.date.issued2017
dc.description.abstractThe 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.neuroscience.2016.10.071pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.22/9495
dc.language.isoengpt_PT
dc.publisherElsevierpt_PT
dc.relation.ispartofseriesNeuroscience;Vol. 340
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0306452216306121pt_PT
dc.subjectEarly life permethrin exposurept_PT
dc.subjectNurr1 promoter methylationpt_PT
dc.subjectDNMTspt_PT
dc.subjecta-synucleinpt_PT
dc.subjectMolecular dockingpt_PT
dc.subjectRatpt_PT
dc.titleIn vivo and in silico studies to identify mechanisms Associated with nurr1 modulation following early Life exposure to permethrin in ratspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage423pt_PT
oaire.citation.startPage411pt_PT
oaire.citation.titleNeurosciencept_PT
oaire.citation.volume340pt_PT
person.familyNameDomingues
person.givenNameValentina Maria Fernandes
person.identifier.ciencia-id4E16-791D-6664
person.identifier.orcid0000-0003-3472-849X
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationbe653ab6-34ec-4329-972a-eee990a7ec66
relation.isAuthorOfPublication.latestForDiscoverybe653ab6-34ec-4329-972a-eee990a7ec66

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