Avaliação dos efeitos do exercício físico associado à suplementação com vitamina D na lesão estriatal unilateral por 6-OHDA em ratos

Detalhes bibliográficos
Ano de defesa: 2022
Autor(a) principal: Costa, Roberta Oliveira da
Orientador(a): Viana, Glauce Socorro de Barros
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/69721
Resumo: Parkinson's disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic cells in the nigrostriatal pathway, with a marked reduction in dopamine (AD) content in the striated body. In the search for new treatment strategies, physical exercise and vitamin D (VD) supplementation has shown numerous benefits for the brain, and can act as a modulator of neurogenesis, neuronal plasticity, besides presenting a strong antioxidant activity. In this scenario, the present study aimed to evaluate the effects of physical exercise associated with VD supplementation on unilateral striatal injury by 6-Hydroxydopamine (6-OHDA) in rats. For this purpose, male Wistar rats were distributed into 6 groups: false operated (FO) without exercise (S/E), false operated (FO) with exercise (C/E), 6-OHDA without exercise (S/E), 6-OHDA with exercise (C/E), 6-OHDA with exercise (S/E) and with VD, 6-OHDA with exercise (C/E) and VD, who received injections of 6-OHDA (12 μg/2μl) or saline solution (FO), in the right striatum through stereotactic surgery. The exercise protocol was performed for 21 days, for 30 min on a treadmill, with a speed of 20 cm/s starting 24 hours after the surgical procedure. Oral administration of VD occurred daily at a volume of 0.1 mL/10 g of weight. The dose used in the animal VD (1μg/kg/day) for 21 days. After the application of treatment protocols, the animals were submitted to behavioral tests (apomorphine, rotarod, open field, cylinder, ymaze, object recognition) and euthanized, the cerebral areas, prefrontal cortex (CPF), hippocampus (HP) and striated body (CE) used for neurochemical and immunohistochemical determinations. Behavioral and neurochemical data were analyzed by the Shapiro-Wilk test to verify normality. The nonparametric data evaluated using the Kruskal-Wallis test followed by Dunn's post-hoc test, while parametric data were analyzed by variance analysis (ANOVA) of a pathway, followed by tukey's post-hoc test for multiple comparations. In all analyses, p<0.05 values were considered statistically significant. The results showed that physical exercise associated with VD supplementation reduced rotational behavior induced by apomorphine, and protected from motor and cognitive deficits (working memory and short duration). In addition, AD levels have increased. As for oxidative stress, it promoted a reduction in malonodialdehyde (MDA) contents and nitrite/nitrate production and increased GSH concentrations. In the immunohistochemical study, physical exercise and VD supplementation prevented the death of dopaminergic neurons in the injured striated body, and increased immunoreactivity for Tyrosine hydroxylase (TH), Dopamine Transporter (DAT) and Glial-derived neurotrophic factor (GDNF). As well as, the inhibition of immunoreactive neurons for glial fibrillar acid protein (GFAP) and Alpha-synuclein. In conclusion, we showed that behavioral and neurochemical changes in Hemiparkinsonian rats were prevented with the application of physical exercise and vd supplementation, attenuating the decrease in AD concentrations in the striatum, characterizing a potential neuroprotective effect in the experimental PD model.
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spelling Costa, Roberta Oliveira daCerqueira, Gilberto SantosViana, Glauce Socorro de Barros2022-12-13T17:28:39Z2022-12-13T17:28:39Z2022-07-28COSTA, R. O. Avaliação dos efeitos do exercício físico associado à suplementação com vitamina D na lesão estriatal unilateral por 6-OHDA em ratos. 2022. 215 f. Tese (Doutorado em Ciências Morfofuncionais) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2022. Disponível em: http://www.repositorio.ufc.br/handle/riufc/69721. Acesso em: 12 dez. 2022.http://www.repositorio.ufc.br/handle/riufc/69721Parkinson's disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic cells in the nigrostriatal pathway, with a marked reduction in dopamine (AD) content in the striated body. In the search for new treatment strategies, physical exercise and vitamin D (VD) supplementation has shown numerous benefits for the brain, and can act as a modulator of neurogenesis, neuronal plasticity, besides presenting a strong antioxidant activity. In this scenario, the present study aimed to evaluate the effects of physical exercise associated with VD supplementation on unilateral striatal injury by 6-Hydroxydopamine (6-OHDA) in rats. For this purpose, male Wistar rats were distributed into 6 groups: false operated (FO) without exercise (S/E), false operated (FO) with exercise (C/E), 6-OHDA without exercise (S/E), 6-OHDA with exercise (C/E), 6-OHDA with exercise (S/E) and with VD, 6-OHDA with exercise (C/E) and VD, who received injections of 6-OHDA (12 μg/2μl) or saline solution (FO), in the right striatum through stereotactic surgery. The exercise protocol was performed for 21 days, for 30 min on a treadmill, with a speed of 20 cm/s starting 24 hours after the surgical procedure. Oral administration of VD occurred daily at a volume of 0.1 mL/10 g of weight. The dose used in the animal VD (1μg/kg/day) for 21 days. After the application of treatment protocols, the animals were submitted to behavioral tests (apomorphine, rotarod, open field, cylinder, ymaze, object recognition) and euthanized, the cerebral areas, prefrontal cortex (CPF), hippocampus (HP) and striated body (CE) used for neurochemical and immunohistochemical determinations. Behavioral and neurochemical data were analyzed by the Shapiro-Wilk test to verify normality. The nonparametric data evaluated using the Kruskal-Wallis test followed by Dunn's post-hoc test, while parametric data were analyzed by variance analysis (ANOVA) of a pathway, followed by tukey's post-hoc test for multiple comparations. In all analyses, p<0.05 values were considered statistically significant. The results showed that physical exercise associated with VD supplementation reduced rotational behavior induced by apomorphine, and protected from motor and cognitive deficits (working memory and short duration). In addition, AD levels have increased. As for oxidative stress, it promoted a reduction in malonodialdehyde (MDA) contents and nitrite/nitrate production and increased GSH concentrations. In the immunohistochemical study, physical exercise and VD supplementation prevented the death of dopaminergic neurons in the injured striated body, and increased immunoreactivity for Tyrosine hydroxylase (TH), Dopamine Transporter (DAT) and Glial-derived neurotrophic factor (GDNF). As well as, the inhibition of immunoreactive neurons for glial fibrillar acid protein (GFAP) and Alpha-synuclein. In conclusion, we showed that behavioral and neurochemical changes in Hemiparkinsonian rats were prevented with the application of physical exercise and vd supplementation, attenuating the decrease in AD concentrations in the striatum, characterizing a potential neuroprotective effect in the experimental PD model.A doença de Parkinson (DP) é uma desordem neurodegenerativa originada pela perda de células dopaminérgicas na via nigroestriatal, com uma acentuada redução no conteúdo de dopamina (DA) no corpo estriado. Na busca de novas estratégias de tratamento, o exercício físico e a suplementação da Vitamina D (VD), tem demostrados numerosos benefícios para o cérebro, podendo atuar como modulador de neurogênese, plasticidade neuronal, além de apresentar uma forte atividade antioxidante. Neste cenário, o presente estudo teve como objetivo avaliar os efeitos do exercício físico associado à suplementação da VD na lesão estriatal unilateral por 6-Hidroxidopamina (6-OHDA) em ratos. Para este fim, ratos machos Wistar foram distribuídos em 6 grupos: falso operado (FO) sem exercício (S/E), falso operado (FO) com exercício (C/E), 6-OHDA sem exercício (S/E), 6-OHDA com exercício (C/E), 6-OHDA com exercício (S/E) e com VD, 6-OHDA com exercício (C/E) e VD, que receberam injeções de 6-OHDA (12 μg/2μl) ou solução salina (FO), no estriado direito através de cirurgia estereotáxica. O protocolo de exercício foi realizado durante 21 dias, por 30 min em esteira, com velocidade de 20 cm/s iniciando-se 24h após o procedimento cirúrgico. A administração oral de VD, aconteceu diariamente no volume de 0,1 mL/10 g de peso. A dose utilizada no animal VD (1µg/kg/dia), por 21 dias. Após a aplicação dos protocolos de tratamento, os animais foram submetidos aos testes comportamentais (apomorfina, rotarod, campo aberto, cilindro, y-maze, reconhecimento de objeto) e eutanasiados, as áreas cerebrais, córtex pré-frontal (CPF), hipocampo (HP) e corpo estriado (CE) utilizados para determinações neuroquímicas e imunohistoquímicas. Os dados foram analisados pelo teste de Shapiro-Wilk para verificar a normalidade. Os dados não paramétricos avaliados através do teste de Kruskal-Wallis seguido do teste post-hoc de Dunn, enquanto, os dados paramétricos foram analisados por análise de variância (ANOVA) de uma via, seguida pelo teste post-hoc de Tukey para comparações múltiplas. Em todas as análises, foram consideradas, estatisticamente significantes, valores de p<0,05. Os resultados evidenciaram que o exercício físico associado à suplementação de VD, reduziu o comportamento rotacional induzido pela apomorfina, e protegeu de déficits motores e cognitivos (memória de trabalho e de curta duração). Além disso, aumentaram os níveis de DA. Quanto ao estresse oxidativo, promoveu uma redução nos conteúdos de malonodialdeído (MDA) e na produção de nitrito/nitrato e aumento das concentrações de GSH. No estudo imunohistoquímico, exercício físico e suplementação de VD preveniu a morte de neurônios dopaminérgicos no corpo estriado lesionado, e aumentou a imunorreatividade para Tirosina hidroxilase (TH), Transportador de Dopamina (DAT) e Fator neurotrófico derivado da glia (GDNF). Assim como, à inibição de neurônios imunorreativos para Proteína glial fibrilar ácida (GFAP) e Alfa-sinucleína. Em conclusão, mostramos que as alterações comportamentais e neuroquímicas em ratos hemiparkinsonianos foram prevenidas com a aplicação do exercício físico e suplementação com VD, atenuaram a diminuição das concentrações de DA no estriado, caracterizando um potencial efeito neuroprotetor no modelo experimental de DP.Doença de ParkinsonExercício FísicoNeuroproteçãoVitamina DOxidopaminaAvaliação dos efeitos do exercício físico associado à suplementação com vitamina D na lesão estriatal unilateral por 6-OHDA em ratosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2022_tese_rocosta.pdf2022_tese_rocosta.pdfapplication/pdf4066745http://repositorio.ufc.br/bitstream/riufc/69721/6/2022_tese_rocosta.pdf1f509be5877026bb82f4faeea415c719MD56LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/69721/7/license.txt8a4605be74aa9ea9d79846c1fba20a33MD57riufc/697212022-12-13 14:39:48.478oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2022-12-13T17:39:48Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Avaliação dos efeitos do exercício físico associado à suplementação com vitamina D na lesão estriatal unilateral por 6-OHDA em ratos
title Avaliação dos efeitos do exercício físico associado à suplementação com vitamina D na lesão estriatal unilateral por 6-OHDA em ratos
spellingShingle Avaliação dos efeitos do exercício físico associado à suplementação com vitamina D na lesão estriatal unilateral por 6-OHDA em ratos
Costa, Roberta Oliveira da
Doença de Parkinson
Exercício Físico
Neuroproteção
Vitamina D
Oxidopamina
title_short Avaliação dos efeitos do exercício físico associado à suplementação com vitamina D na lesão estriatal unilateral por 6-OHDA em ratos
title_full Avaliação dos efeitos do exercício físico associado à suplementação com vitamina D na lesão estriatal unilateral por 6-OHDA em ratos
title_fullStr Avaliação dos efeitos do exercício físico associado à suplementação com vitamina D na lesão estriatal unilateral por 6-OHDA em ratos
title_full_unstemmed Avaliação dos efeitos do exercício físico associado à suplementação com vitamina D na lesão estriatal unilateral por 6-OHDA em ratos
title_sort Avaliação dos efeitos do exercício físico associado à suplementação com vitamina D na lesão estriatal unilateral por 6-OHDA em ratos
author Costa, Roberta Oliveira da
author_facet Costa, Roberta Oliveira da
author_role author
dc.contributor.co-advisor.none.fl_str_mv Cerqueira, Gilberto Santos
dc.contributor.author.fl_str_mv Costa, Roberta Oliveira da
dc.contributor.advisor1.fl_str_mv Viana, Glauce Socorro de Barros
contributor_str_mv Viana, Glauce Socorro de Barros
dc.subject.por.fl_str_mv Doença de Parkinson
Exercício Físico
Neuroproteção
Vitamina D
Oxidopamina
topic Doença de Parkinson
Exercício Físico
Neuroproteção
Vitamina D
Oxidopamina
description Parkinson's disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic cells in the nigrostriatal pathway, with a marked reduction in dopamine (AD) content in the striated body. In the search for new treatment strategies, physical exercise and vitamin D (VD) supplementation has shown numerous benefits for the brain, and can act as a modulator of neurogenesis, neuronal plasticity, besides presenting a strong antioxidant activity. In this scenario, the present study aimed to evaluate the effects of physical exercise associated with VD supplementation on unilateral striatal injury by 6-Hydroxydopamine (6-OHDA) in rats. For this purpose, male Wistar rats were distributed into 6 groups: false operated (FO) without exercise (S/E), false operated (FO) with exercise (C/E), 6-OHDA without exercise (S/E), 6-OHDA with exercise (C/E), 6-OHDA with exercise (S/E) and with VD, 6-OHDA with exercise (C/E) and VD, who received injections of 6-OHDA (12 μg/2μl) or saline solution (FO), in the right striatum through stereotactic surgery. The exercise protocol was performed for 21 days, for 30 min on a treadmill, with a speed of 20 cm/s starting 24 hours after the surgical procedure. Oral administration of VD occurred daily at a volume of 0.1 mL/10 g of weight. The dose used in the animal VD (1μg/kg/day) for 21 days. After the application of treatment protocols, the animals were submitted to behavioral tests (apomorphine, rotarod, open field, cylinder, ymaze, object recognition) and euthanized, the cerebral areas, prefrontal cortex (CPF), hippocampus (HP) and striated body (CE) used for neurochemical and immunohistochemical determinations. Behavioral and neurochemical data were analyzed by the Shapiro-Wilk test to verify normality. The nonparametric data evaluated using the Kruskal-Wallis test followed by Dunn's post-hoc test, while parametric data were analyzed by variance analysis (ANOVA) of a pathway, followed by tukey's post-hoc test for multiple comparations. In all analyses, p<0.05 values were considered statistically significant. The results showed that physical exercise associated with VD supplementation reduced rotational behavior induced by apomorphine, and protected from motor and cognitive deficits (working memory and short duration). In addition, AD levels have increased. As for oxidative stress, it promoted a reduction in malonodialdehyde (MDA) contents and nitrite/nitrate production and increased GSH concentrations. In the immunohistochemical study, physical exercise and VD supplementation prevented the death of dopaminergic neurons in the injured striated body, and increased immunoreactivity for Tyrosine hydroxylase (TH), Dopamine Transporter (DAT) and Glial-derived neurotrophic factor (GDNF). As well as, the inhibition of immunoreactive neurons for glial fibrillar acid protein (GFAP) and Alpha-synuclein. In conclusion, we showed that behavioral and neurochemical changes in Hemiparkinsonian rats were prevented with the application of physical exercise and vd supplementation, attenuating the decrease in AD concentrations in the striatum, characterizing a potential neuroprotective effect in the experimental PD model.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-12-13T17:28:39Z
dc.date.available.fl_str_mv 2022-12-13T17:28:39Z
dc.date.issued.fl_str_mv 2022-07-28
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dc.identifier.citation.fl_str_mv COSTA, R. O. Avaliação dos efeitos do exercício físico associado à suplementação com vitamina D na lesão estriatal unilateral por 6-OHDA em ratos. 2022. 215 f. Tese (Doutorado em Ciências Morfofuncionais) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2022. Disponível em: http://www.repositorio.ufc.br/handle/riufc/69721. Acesso em: 12 dez. 2022.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/69721
identifier_str_mv COSTA, R. O. Avaliação dos efeitos do exercício físico associado à suplementação com vitamina D na lesão estriatal unilateral por 6-OHDA em ratos. 2022. 215 f. Tese (Doutorado em Ciências Morfofuncionais) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2022. Disponível em: http://www.repositorio.ufc.br/handle/riufc/69721. Acesso em: 12 dez. 2022.
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