Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and alpha-Synuclein Expression

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dc.citation.volume9
dc.contributor.authorLeão, Anderson Henrique França Figueiredo [UNIFESP]
dc.contributor.authorMeurer, Ywlliane da Silva Rodrigues
dc.contributor.authorSilva, Anatildes Feitosa
dc.contributor.authorMedeiros, André de Macêdo [UNIFESP]
dc.contributor.authorCampelo, Clarissa Loureiro Chagas
dc.contributor.authorAbílio, Vanessa Costhek [UNIFESP]
dc.contributor.authorEngelberth, Rovena Clara Galvão Januário
dc.contributor.authorCavalcante, Jeferson de Souza
dc.contributor.authorIzídio, Geison Souza
dc.contributor.authorRibeiro, Alessandra Mussi [UNIFESP]
dc.contributor.authorSilva, Regina Helena [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.coverageLausanne
dc.date.accessioned2020-07-17T14:02:37Z
dc.date.available2020-07-17T14:02:37Z
dc.date.issued2017
dc.description.abstractReserpine is an irreversible inhibitor of vesicular monoamine transporter-2 (VMAT2) used to study Parkinson's disease (PD) and screening for antiparkinsonian treatments in rodents. Recently, the repeated treatment with a low-dose of reserpine was proposed as a progressive model of PD. Rats under this treatment show progressive catalepsy behavior, oral movements and spontaneous motor activity decrement. In parallel, compared to Wistar rats, spontaneously hypertensive rats (SHR) are resistant to acute reserpine-induced oral dyskinesia. We aimed to assess whether SHR would present differential susceptibility to repeated reserpine-induced deficits in the progressive model of PD. Male Wistar and SHR rats were administered 15 subcutaneously (s.c.) injections of reserpine (0.1 mgkg) or vehicle, every other day and motor activity was assessed by the catalepsy, oral movements and open field tests. Only reserpine-treated Wistar rats presented increased latency to step down in the catalepsy test and impaired spontaneous activity in the open field. On the other hand, there was an increase in oral movements in both reserpine-treated strains, although with reduced magnitude and latency to instauration in SHR. After a 15-day withdrawn period, both strains recovered from motor impairment, but SHR animals expressed reduced latencies to reach control levels. Finally, we performed immunohistochemistry for tyrosine hydroxylase (TH) and a-synuclein (alpha-syn) 48 h after the last injection or 15 days after withdrawn. Reserpinetreated animals presented a reduction in TH and an increase in alpha-syn immunoreactivity in the substantia nigra and dorsal striatum (dSTR), which were both recovered after 15 days of withdraw. Furthermore, SHR rats were resistant to reserpine-induced TH decrement in the substantia nigra, and presented reduced immunoreactivity to a-syn inthe dSTR relative to Wistar rats, irrespective of treatment. This effect was accompanied by increase of malondaldhyde (MDA) in the striatum of reserpine-treated Wistar rats, while SHR presented reduced MDA in both control and reserpine conditions relative to Wistar strain. In conclusion, the current results show that SHR are resilient to motor and neurochemical impairments induced by the repeated low-dose reserpine protocol. These findings indicate that the neurochemical, molecular and genetic differences in the SHR strain are potential relevant targets to the study of susceptibility to PD.en
dc.description.affiliationUniv Fed Rio Grande do Norte, Dept Physiol, Memory Studies Lab, Natal, RN, Brazil
dc.description.affiliationUniv Fed Rio Grande do Norte, Brain Inst, Natal, RN, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Pharmacol, Behav Neurosci Lab, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Rio Grande do Norte, Dept Physiol, Neurochem Studies Lab, Natal, RN, Brazil
dc.description.affiliationUniv Santa Catarina, Dept Cellular Biol Embryol & Genet, Lab Behav Genet, Florianopolis, SC, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biosci, Santos, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Pharmacol, Behav Neurosci Lab, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biosci, Santos, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt
dc.description.sponsorshipFundação de Apoio à Pesquisa do Estado do Rio Grande do Norte (FAPERN)pt
dc.description.sponsorshipPró-reitoria de Pesquisa da Universidade Federal do Rio Grande do Norte (PROPESQ/UFRN)pt
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipIDFAPESP: 2015/12308-5pt
dc.description.sponsorshipIDFAPESP: 2015/03354-3pt
dc.identifierhttps://dx.doi.org/10.3389/fnagi.2017.00078
dc.identifier.citationFrontiers In Aging Neuroscience. Lausanne, v. 9, p. -, 2017.
dc.identifier.doi10.3389/fnagi.2017.00078
dc.identifier.fileWOS000397394200001.pdf
dc.identifier.issn1663-4365
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54908
dc.identifier.wosWOS:000397394200001
dc.language.isoeng
dc.publisherFrontiers Media Sa
dc.relation.ispartofFrontiers In Aging Neuroscience
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectReserpineen
dc.subjectParkinson's diseaseen
dc.subjectSHRen
dc.subjectAlpha-synucleinen
dc.subjectTyrosine hydroxylaseen
dc.titleSpontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and alpha-Synuclein Expressionen
dc.typeinfo:eu-repo/semantics/article
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