Papel da vitamina D3 em doenças neurológicas e avaliação pré-clinica na demência esporádica do tipo Alzheimer
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/20334 |
Resumo: | Dementia is a brain disorder characterized by decline of some function, resulting in deficits in memory functioning and in dialy cognitive tasks. Evidence has emerged that Vitamin D3 (VD3) has innumerable functions in the Central Nervous System (CNS) such as: neuroprotection and neuroimmunomodulation, besides having antioxidante function. Thus, the objective of our study was to investigate the role of VD3 on memory and oxidative stress in a model of sporadic dementia of Azlheimer’s type (SDAT), induced by intracerebroventricular administration of Streptozotocin (ICV-STZ). In addition, a literature review was also performed on the assossiation of VD3 in some neurogocnitive disorders such as: Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Multiple Sclerosis (MS) and Schizophrenia (SZ). The analyzes where performed in through two experiments. In the first experimental research, 56 adults male Wistar rats were used, and in the second experimental research, 40 adults male Wistar rats were used. Both animals were submitted to a cirurgical procedure for the administratios of ICV-STZ (3 mg/ kg), to in a order to induce demetia in these animals, and after birding for a recovery of 3 days and after oral doses of VD3 for 21 days. In the forst experiment the animals were divided into 8 groups: CTL (control), CTL + 12,5 µg/kg, CTL + 42 µg/kg, CTL + 125 µg/kg, STZ (streptozotocin); STZ + 12,5 µg/kg, STZ + 42 µg/kg, STZ + 125 µg/kg. In the second experiment, animals were divided into 4 groups: CTL, CTL + 125 µg/kg, STZ, STZ + 125 µg/kg. The results obtained in theses experiments demonstrated in relation to the activity of the enzyme acetylcholinesterase (AChE) in cerebral cortex supernatant a significant increase in the groups if aniumals that receiving ICV-STZ, with the doses of 42 µg/kg e 125 µg/kg of VD3 were able to prevent this increase, whereas with regard to AChE activity in cerebral cortex of synaptossomes, a significant increase was alsoobserved in animals receiving ICV-STZ, with a dose of 125 µg/kg of VD3 capable of of preventing this increase. Moreover, in theses same animals an increase in thiobarbituric acid levels (TBARS) was found, and the dose of 125 µg/kg able to prevent, similarly with regard to carbonil protein levels in the animals with ICV-STZ a significant increase, with doses 12,5 µg/kg, 42 µg/kg e 125 µg/kg of VD3 being able to prevent. Regarding the levels of reative species of oxigen (ROS, we did not observed significant difference in the animals that dementia. In congtrast, we observed a reduction in Vitamin C levels, however VD3 was not able to predict this result. Regarding reduced Gluathione (GSH), a significant reduction was observed in animals receiving ICV-STZ, with a dose of 125 µg/kg of VD3 capable of preventing in contrast, an ncrease an oxided Gluthatione (GSSG) levels was found. The doses of 12,5 µg/kg, 42 µg/kg e 125 µg/kg of VD3 were able to prevent this increase. Likewise, a significant increase was observed in relation to the thiol groups in the animals receiving ICV-STZ doses of 42 µg/kg e 125 µg/kg of VD3 capable of prevention. Finally, regarding behavioral test results, treatment with VD3 reversed animal damage caused by ICV-STZ in the Morris Water Mazze (MWM) test, in both time spent in the quadrant target, a significant increase was observed in animals receiving ICV-STZ, with a dose of 125 µg/kg of VD3 being alble to prevent. Regarding the number of intersections in the target quadrant, no significant difference was observed in between the groups. In the time spent in the quadrant something during the test day a significant reduction was observed in the animals received ICV-STZ, with the 125 iµg/kg of VD3 being albe to prevent this reduction and finally, regarding the number of crossings in the target quadrant in test day no difference was observed between the groups. These results demonstrat e the high levels of oxidative stress, in adittion to behavioral decline presented by animals with dementia, and the treatmente of VD3 can prevent this decline. Regarding to literature review on neurocognitive diseases (AD, PD, MS and SZ), it is believe that decrease levels of VD3 may be related to the onset of theses diseases. In contrast, the supplementation wich this Vitamin can have beneficial effects by the preventing the damage caused by these diseases. Thus, we can suggest that this compund can be used as a new suppoting strategy to control and prevent conginitive dysfunctions associasted with neurodegenerative and neurocognitive disorders. |
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Papel da vitamina D3 em doenças neurológicas e avaliação pré-clinica na demência esporádica do tipo AlzheimerRole of vitamin dDn neurological diseases and pré-clinical evaluation in sporadic dementia of Alzheimer’s typeVitamina D3MemóriaEstresse oxidativoDemênciaDoenças neurocognitivasCNPQ::CIENCIAS BIOLOGICASDementia is a brain disorder characterized by decline of some function, resulting in deficits in memory functioning and in dialy cognitive tasks. Evidence has emerged that Vitamin D3 (VD3) has innumerable functions in the Central Nervous System (CNS) such as: neuroprotection and neuroimmunomodulation, besides having antioxidante function. Thus, the objective of our study was to investigate the role of VD3 on memory and oxidative stress in a model of sporadic dementia of Azlheimer’s type (SDAT), induced by intracerebroventricular administration of Streptozotocin (ICV-STZ). In addition, a literature review was also performed on the assossiation of VD3 in some neurogocnitive disorders such as: Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Multiple Sclerosis (MS) and Schizophrenia (SZ). The analyzes where performed in through two experiments. In the first experimental research, 56 adults male Wistar rats were used, and in the second experimental research, 40 adults male Wistar rats were used. Both animals were submitted to a cirurgical procedure for the administratios of ICV-STZ (3 mg/ kg), to in a order to induce demetia in these animals, and after birding for a recovery of 3 days and after oral doses of VD3 for 21 days. In the forst experiment the animals were divided into 8 groups: CTL (control), CTL + 12,5 µg/kg, CTL + 42 µg/kg, CTL + 125 µg/kg, STZ (streptozotocin); STZ + 12,5 µg/kg, STZ + 42 µg/kg, STZ + 125 µg/kg. In the second experiment, animals were divided into 4 groups: CTL, CTL + 125 µg/kg, STZ, STZ + 125 µg/kg. The results obtained in theses experiments demonstrated in relation to the activity of the enzyme acetylcholinesterase (AChE) in cerebral cortex supernatant a significant increase in the groups if aniumals that receiving ICV-STZ, with the doses of 42 µg/kg e 125 µg/kg of VD3 were able to prevent this increase, whereas with regard to AChE activity in cerebral cortex of synaptossomes, a significant increase was alsoobserved in animals receiving ICV-STZ, with a dose of 125 µg/kg of VD3 capable of of preventing this increase. Moreover, in theses same animals an increase in thiobarbituric acid levels (TBARS) was found, and the dose of 125 µg/kg able to prevent, similarly with regard to carbonil protein levels in the animals with ICV-STZ a significant increase, with doses 12,5 µg/kg, 42 µg/kg e 125 µg/kg of VD3 being able to prevent. Regarding the levels of reative species of oxigen (ROS, we did not observed significant difference in the animals that dementia. In congtrast, we observed a reduction in Vitamin C levels, however VD3 was not able to predict this result. Regarding reduced Gluathione (GSH), a significant reduction was observed in animals receiving ICV-STZ, with a dose of 125 µg/kg of VD3 capable of preventing in contrast, an ncrease an oxided Gluthatione (GSSG) levels was found. The doses of 12,5 µg/kg, 42 µg/kg e 125 µg/kg of VD3 were able to prevent this increase. Likewise, a significant increase was observed in relation to the thiol groups in the animals receiving ICV-STZ doses of 42 µg/kg e 125 µg/kg of VD3 capable of prevention. Finally, regarding behavioral test results, treatment with VD3 reversed animal damage caused by ICV-STZ in the Morris Water Mazze (MWM) test, in both time spent in the quadrant target, a significant increase was observed in animals receiving ICV-STZ, with a dose of 125 µg/kg of VD3 being alble to prevent. Regarding the number of intersections in the target quadrant, no significant difference was observed in between the groups. In the time spent in the quadrant something during the test day a significant reduction was observed in the animals received ICV-STZ, with the 125 iµg/kg of VD3 being albe to prevent this reduction and finally, regarding the number of crossings in the target quadrant in test day no difference was observed between the groups. These results demonstrat e the high levels of oxidative stress, in adittion to behavioral decline presented by animals with dementia, and the treatmente of VD3 can prevent this decline. Regarding to literature review on neurocognitive diseases (AD, PD, MS and SZ), it is believe that decrease levels of VD3 may be related to the onset of theses diseases. In contrast, the supplementation wich this Vitamin can have beneficial effects by the preventing the damage caused by these diseases. Thus, we can suggest that this compund can be used as a new suppoting strategy to control and prevent conginitive dysfunctions associasted with neurodegenerative and neurocognitive disorders.A demência é uma desordem cerebral caracterizada pelo declínio de algumas funções mentais, resultando em déficits no funcionamento da memória e em tarefas cognitivas diárias. Evidências têm surgerido que a Vitamina D3 (VD3) possui inúmeras funções no Sistema Nervoso Central (SNC), tais como: neuroproteção e neuroimunomoduação, além de possuir ação antioxidante. Dessa forma, o objetivo deste trabalho foi investigar o papel da VD3 sobre a memória e o estresse oxidativo em ratos submetidos a um modelo de Demencia Esporádica do Tipo Alzheimer (DETA) em ratos, induzida pela administração intracerebroventricular de estreptozotocina (ICV-STZ). Em adição também foi realizada uma revisão de literatura sobre a associação da VD3 em alguns desordens neurocognitivos como: Doença de Alzheimer (DA), Doença de Parkinson (DP), Esclerose Múltipla (EM) e Esquizofrenia (ES). As análises foram realizadas em através dois experimentos. No primeira pesquisa experimental, foram utilizados 56 ratos wistar machos adultos, e na segunda pesquisa experimental foram utilizados 40 ratos Wistar machos adultos, em ambos os animais foram submetidos a um procedimento cirúrgico para a administração da ICV-STZ (3 mg/kg) a fim de induzir a demência nesses animais, sendo que após pássaram por um período de recuperação da cirurgia de 3 dias e após receram as doses de VD3 via oral por 21 dias. No primeiro experimentos os animais foram divididos em 8 grupos, conforme as diferentes doses: CTL (controle), CTL + 12,5 µg/kg, CTL + 42 µg/kg, CTL + 125 µg/kg, STZ (streptozotocina); STZ + 12,5 µg/kg, STZ + 42 µg/kg, STZ + 125 µg/kg. Já no segundo experimento os animais foram divididos em 4 grupos: CTL, CTL + 125 µg/kg, STZ, STZ + 125 µg/kg. Os resultados obtidos nestes experimentos demonstraram em relação à atividade da enzima acetilcolinesterase (AChE) em sobrenadante de córtex cerebral um aumento significativo nos grupos de animais que receberam ICV-STZ, sendo que as doses de 42 µg/kg e 125 µg/kg de VD3 foram capazes de previnir esse aumento, já com relação a atividade da AchE em sinaptossomas de córtex cerebral também foi observado um aumento significativo nos animais que receberam ICV-STZ, sendo a dose de 125 µg/kg de VD3 capaz de previnir esse aumento. Além disso, nesses mesmos animais foi encontrado um aumento dos níveis de ácido tiobarbitúrico (TBARS), sendo a dose de 125 µg/kg capaz de previnir, da mesma forma, com relação aos níveis de proteína carbonil nos animais com ICV-STZ foi observado um aumento significativo, sendo as doses de 12,5 µg/kg, 42 µg/kg e 125 µg/kg de VD3 capazes de previnir. Com relação aos níveis de espécies reativas de oxigênio (ROS), não observamos diferença significativa nos animais com demência. Em contrapartida, observamos uma redução nos níveis de Vitamina C, entretanto a VD3 não foi capaz de previr esse resultado. Em relação a Glutationa Reduzida (GSH), foi observado uma redução significativa nos animais que receram ICV-STZ, sendo a dose de 125 µg/kg de VD3 capaz de previnir, em contrapartida foi encontrado um aumento nos níveis de Glutationa Oxidada (GSSG), sendo as doses de 12,5 µg/kg, 42 µg/kg e 125 µg/kg capazes de previnir esse aumento, da mesma forma foi observado um aumento significativos com relação aos grupos Tióis nos animais que receberam ICV-STZ, sendo as doses de 42 µg/kg e 125 µg/kg de VD3 capazes de previnir. Finalmente, com relação aos resultados dos testes comportamentais, o tratamento com VD3 reverteu danos causados em animais pela ICV-STZ no teste de Labirinto de Morris Water Maze (MWM), sendo que em ambos: tempo para encontrar a plataforma e tempo gasto no quadrante alvo, foi observado um aumento significativo nos animais que receberam ICV-STZ, sendo a dose de 125 µg/kg de VD3 foi capaz de previnir. Com relação ao número de cruzamentos no quadrante alvo não foi observado diferença significativa entre os grupos. No tempo gasto no quadrante algo durante o dia teste foi observado uma redução significativa nos animais que receberam ICV-STZ, sendo a dose 125 µg/kg de VD3 capaz de previnir essa redução e finalmente, com relação ao número de cruzamentos no quadrante alvo no dia teste não foi observado diferença entre os grupos. Esses resultados demostram os altos níveis de estresse oxidativo, alem do declínio comportamental apresentado pelos animais com demência, sendo o tratamento com VD3 capaz de prevenir esse declínio. Com relação revisão literária sobre às doenças neurocognitivas (DA, DP, DH e ES), acredita-se que níveis diminuídos da VD3 podem estar relacionados ao surgimento dessas doenças. Em contrapartida, a suplementação com essa Vitamina pode ter efeitos benéficos, prevenindo os danos causados por essas doenças. Dessa forma, podemos sugerir que este composto pode ser utilizado como uma nova estratégia coadjuvante para controlar e prevenir disfunções cognitivas associado a doenças neurodegenerativas e neurocognitivas.Universidade Federal de Santa MariaBrasilCiências BiológicasUFSMPrograma de Pós-Graduação em AdministraçãoCentro de Ciências Naturais e ExatasAndrade, Cinthia Melazzo deGutierres, Jessié Martinshttp://lattes.cnpq.br/2886709251370905Spanevello, Roselia MariaLeal, Marta Lizandra do RegoStefanello, Francielli MoroBagatini, Margarete DulceRodrigues, Marília Valvassori2021-02-25T18:57:22Z2021-02-25T18:57:22Z2019-09-06info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/20334porna integra na teseAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2021-09-29T19:53:02Zoai:repositorio.ufsm.br:1/20334Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-09-29T19:53:02Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Papel da vitamina D3 em doenças neurológicas e avaliação pré-clinica na demência esporádica do tipo Alzheimer Role of vitamin dDn neurological diseases and pré-clinical evaluation in sporadic dementia of Alzheimer’s type |
title |
Papel da vitamina D3 em doenças neurológicas e avaliação pré-clinica na demência esporádica do tipo Alzheimer |
spellingShingle |
Papel da vitamina D3 em doenças neurológicas e avaliação pré-clinica na demência esporádica do tipo Alzheimer Rodrigues, Marília Valvassori Vitamina D3 Memória Estresse oxidativo Demência Doenças neurocognitivas CNPQ::CIENCIAS BIOLOGICAS |
title_short |
Papel da vitamina D3 em doenças neurológicas e avaliação pré-clinica na demência esporádica do tipo Alzheimer |
title_full |
Papel da vitamina D3 em doenças neurológicas e avaliação pré-clinica na demência esporádica do tipo Alzheimer |
title_fullStr |
Papel da vitamina D3 em doenças neurológicas e avaliação pré-clinica na demência esporádica do tipo Alzheimer |
title_full_unstemmed |
Papel da vitamina D3 em doenças neurológicas e avaliação pré-clinica na demência esporádica do tipo Alzheimer |
title_sort |
Papel da vitamina D3 em doenças neurológicas e avaliação pré-clinica na demência esporádica do tipo Alzheimer |
author |
Rodrigues, Marília Valvassori |
author_facet |
Rodrigues, Marília Valvassori |
author_role |
author |
dc.contributor.none.fl_str_mv |
Andrade, Cinthia Melazzo de Gutierres, Jessié Martins http://lattes.cnpq.br/2886709251370905 Spanevello, Roselia Maria Leal, Marta Lizandra do Rego Stefanello, Francielli Moro Bagatini, Margarete Dulce |
dc.contributor.author.fl_str_mv |
Rodrigues, Marília Valvassori |
dc.subject.por.fl_str_mv |
Vitamina D3 Memória Estresse oxidativo Demência Doenças neurocognitivas CNPQ::CIENCIAS BIOLOGICAS |
topic |
Vitamina D3 Memória Estresse oxidativo Demência Doenças neurocognitivas CNPQ::CIENCIAS BIOLOGICAS |
description |
Dementia is a brain disorder characterized by decline of some function, resulting in deficits in memory functioning and in dialy cognitive tasks. Evidence has emerged that Vitamin D3 (VD3) has innumerable functions in the Central Nervous System (CNS) such as: neuroprotection and neuroimmunomodulation, besides having antioxidante function. Thus, the objective of our study was to investigate the role of VD3 on memory and oxidative stress in a model of sporadic dementia of Azlheimer’s type (SDAT), induced by intracerebroventricular administration of Streptozotocin (ICV-STZ). In addition, a literature review was also performed on the assossiation of VD3 in some neurogocnitive disorders such as: Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Multiple Sclerosis (MS) and Schizophrenia (SZ). The analyzes where performed in through two experiments. In the first experimental research, 56 adults male Wistar rats were used, and in the second experimental research, 40 adults male Wistar rats were used. Both animals were submitted to a cirurgical procedure for the administratios of ICV-STZ (3 mg/ kg), to in a order to induce demetia in these animals, and after birding for a recovery of 3 days and after oral doses of VD3 for 21 days. In the forst experiment the animals were divided into 8 groups: CTL (control), CTL + 12,5 µg/kg, CTL + 42 µg/kg, CTL + 125 µg/kg, STZ (streptozotocin); STZ + 12,5 µg/kg, STZ + 42 µg/kg, STZ + 125 µg/kg. In the second experiment, animals were divided into 4 groups: CTL, CTL + 125 µg/kg, STZ, STZ + 125 µg/kg. The results obtained in theses experiments demonstrated in relation to the activity of the enzyme acetylcholinesterase (AChE) in cerebral cortex supernatant a significant increase in the groups if aniumals that receiving ICV-STZ, with the doses of 42 µg/kg e 125 µg/kg of VD3 were able to prevent this increase, whereas with regard to AChE activity in cerebral cortex of synaptossomes, a significant increase was alsoobserved in animals receiving ICV-STZ, with a dose of 125 µg/kg of VD3 capable of of preventing this increase. Moreover, in theses same animals an increase in thiobarbituric acid levels (TBARS) was found, and the dose of 125 µg/kg able to prevent, similarly with regard to carbonil protein levels in the animals with ICV-STZ a significant increase, with doses 12,5 µg/kg, 42 µg/kg e 125 µg/kg of VD3 being able to prevent. Regarding the levels of reative species of oxigen (ROS, we did not observed significant difference in the animals that dementia. In congtrast, we observed a reduction in Vitamin C levels, however VD3 was not able to predict this result. Regarding reduced Gluathione (GSH), a significant reduction was observed in animals receiving ICV-STZ, with a dose of 125 µg/kg of VD3 capable of preventing in contrast, an ncrease an oxided Gluthatione (GSSG) levels was found. The doses of 12,5 µg/kg, 42 µg/kg e 125 µg/kg of VD3 were able to prevent this increase. Likewise, a significant increase was observed in relation to the thiol groups in the animals receiving ICV-STZ doses of 42 µg/kg e 125 µg/kg of VD3 capable of prevention. Finally, regarding behavioral test results, treatment with VD3 reversed animal damage caused by ICV-STZ in the Morris Water Mazze (MWM) test, in both time spent in the quadrant target, a significant increase was observed in animals receiving ICV-STZ, with a dose of 125 µg/kg of VD3 being alble to prevent. Regarding the number of intersections in the target quadrant, no significant difference was observed in between the groups. In the time spent in the quadrant something during the test day a significant reduction was observed in the animals received ICV-STZ, with the 125 iµg/kg of VD3 being albe to prevent this reduction and finally, regarding the number of crossings in the target quadrant in test day no difference was observed between the groups. These results demonstrat e the high levels of oxidative stress, in adittion to behavioral decline presented by animals with dementia, and the treatmente of VD3 can prevent this decline. Regarding to literature review on neurocognitive diseases (AD, PD, MS and SZ), it is believe that decrease levels of VD3 may be related to the onset of theses diseases. In contrast, the supplementation wich this Vitamin can have beneficial effects by the preventing the damage caused by these diseases. Thus, we can suggest that this compund can be used as a new suppoting strategy to control and prevent conginitive dysfunctions associasted with neurodegenerative and neurocognitive disorders. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-09-06 2021-02-25T18:57:22Z 2021-02-25T18:57:22Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/20334 |
url |
http://repositorio.ufsm.br/handle/1/20334 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
na integra na tese |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Ciências Biológicas UFSM Programa de Pós-Graduação em Administração Centro de Ciências Naturais e Exatas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Ciências Biológicas UFSM Programa de Pós-Graduação em Administração Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1805922042159038464 |