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Aline Silva de Mirandahttp://lattes.cnpq.br/4102666350497478Dr. Victor Rodrigues SantosDr. Thiago Verano BragaDra. Erica VieiraDra. Milene Alvarenga Rachidhttps://lattes.cnpq.br/5015424176229572Bruna da Silva Oliveira2024-02-27T16:17:31Z2024-02-27T16:17:31Z2023-10-31http://hdl.handle.net/1843/64795https://orcid.org/0000-0003-1121-4015A doença de Parkinson (DP) é classicamente caracterizada por alterações motoras, como tremor de repouso, bradicinesia, rigidez e instabilidade postural, relacionados à perda de neurônios dopaminérgicos na substância nigra pars compacta (SNpc). A diminuição de dopamina também afeta núcleos não dopaminérgicos, levando a sintomas não motores relacionados à DP (SNDP), que podem aparecer até 25 anos antes dos sintomas motores. Embora SNDP reduzam a qualidade de vida dos pacientes com DP, os mecanismos que desencadeiam esses sintomas permanecem pouco esclarecidos. Pesquisas anteriores têm identificado a presença do Sistema Renina-Angiotensina (SRA) no encéfalo, levantando a hipótese de que componentes do SRA podem desempenhar um papel nas doenças neurodegenerativas, incluindo a DP. O objetivo principal do presente estudo foi investigar o potencial envolvimento do SRA em SNMDP. Primeiro, com objetivo de padronizar um modelo prodrômico da DP administramos 1-metil-4-fenil-1,2,3,6-tetrahidropiridina (MPTP) ou uma solução salina por via intranasal em camundongos C57BL/6 machos. Em seguida, realizamos uma ampla avaliação comportamental e analisamos marcadores neuroinflamatórios e dopaminérgicos em áreas chaves da DP, como SNpc e o Estriado. Uma vez estabelecido o modelo prodrômico da DP, conduzimos novos experimentos para investigar o papel do SRA nos SNMDP. Dividimos os camundongos C57BL/6 machos em cinco grupos, incluindo um grupo MPTP que recebeu solução salina a 0,9%. Os outros grupos receberam tratamentos específicos: Perindopril (5mg/Kg, um antagonista da enzima conversora de angiotensina (ECA), Telmisartan (10mg/Kg, um antagonista dos receptores AT1) e AVE099 (10mg/Kg, um agonista dos receptores Mas), administrados por gavagem. Esses tratamentos começaram cinco dias antes da infusão de MPTP e continuaram até o 11º dia após a infusão. Nossos resultados revelaram uma melhora significativa em parâmetros comportamentais, inflamatórios e neuroquímicos nos animais tratados com o AVE0991, indicando uma potencial neuroproteção conferida pelo eixo alternativo do SRA na DP experimental.Parkinson's disease (PD) is classically conceived as a motor condition characterized resting tremor, bradykinesia, rigidity and postural instability, related to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The decrease in dopamine also affects non-dopaminergic nuclei, leading to non-motor symptoms related to PD (NMS-PD), which can appear up to 25 years before the motor symptoms. Although NMS-PD reduce the quality of life of PD patients, the mechanisms underlying the development of these symptoms remain poorly understood. Previous research has identified the presence of the Renin-Angiotensin System (RAS) in the brain, raising the hypothesis that RAS molecules may play a role in neurodegenerative diseases, including PD. The main goal of this study was to investigate the potential involvement of the RAS in NMS-PD. First, with the aim of standardizing a prodromal model of PD, we administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or a saline solution intranasally to male C57BL/6 mice. Subsequently, we conducted a comprehensive behavioral assessment and analyzed neuroinflammatory and dopaminergic markers in key areas of PD, such as the SNpc and the Striatum. After this characterization, we conducted new experiments to investigate the role of RAS components in NMS-PD. We divided male C57BL/6 mice into five groups, including a MPTP group that received 0.9% saline. The other groups received specific treatments: Perindopril (5mg/Kg, an angiotensin-converting enzyme (ACE) inhibitor), Telmisartan (10mg/Kg, an AT1 receptor antagonist), and AVE099 (10mg/Kg, a Mas receptor agonist), administered by gavage. These treatments began five days before MPTP infusion and continued until the 11th day after infusion. Our results revealed a significant improvement in behavioral, inflammatory, and neurochemical parameters in animals treated with AVE0991, indicating a potential neuroprotective role of RAS alternative axis in experimental PD.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Biologia CelularUFMGBrasilICB - DEPARTAMENTO DE MORFOLOGIABiologia CelularDoença de ParkinsonSistema Renina-AngiotensinaInflamaçãoDoença de ParkinsonSistema Renina AngiotensinaMPTPNeuroinflamaçãoCaracterização de um modelo prodrômico da Doença de Parkinson e estudo do efeito de moduladores do sistema Renina-Angiotensinainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINAL(Tese) Bruna Oliveira.pdf(Tese) Bruna Oliveira.pdfapplication/pdf7624984https://repositorio.ufmg.br/bitstream/1843/64795/1/%28Tese%29%20Bruna%20Oliveira.pdfdc7a72618fdb2d8dbe3130bf464afdd6MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82118https://repositorio.ufmg.br/bitstream/1843/64795/2/license.txtcda590c95a0b51b4d15f60c9642ca272MD521843/647952024-02-27 13:17:31.549oai:repositorio.ufmg.br:1843/64795TElDRU7Dh0EgREUgRElTVFJJQlVJw4fDg08gTsODTy1FWENMVVNJVkEgRE8gUkVQT1NJVMOTUklPIElOU1RJVFVDSU9OQUwgREEgVUZNRwoKQ29tIGEgYXByZXNlbnRhw6fDo28gZGVzdGEgbGljZW7Dp2EsIHZvY8OqIChvIGF1dG9yIChlcykgb3UgbyB0aXR1bGFyIGRvcyBkaXJlaXRvcyBkZSBhdXRvcikgY29uY2VkZSBhbyBSZXBvc2l0w7NyaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIChSSS1VRk1HKSBvIGRpcmVpdG8gbsOjbyBleGNsdXNpdm8gZSBpcnJldm9nw6F2ZWwgZGUgcmVwcm9kdXppciBlL291IGRpc3RyaWJ1aXIgYSBzdWEgcHVibGljYcOnw6NvIChpbmNsdWluZG8gbyByZXN1bW8pIHBvciB0b2RvIG8gbXVuZG8gbm8gZm9ybWF0byBpbXByZXNzbyBlIGVsZXRyw7RuaWNvIGUgZW0gcXVhbHF1ZXIgbWVpbywgaW5jbHVpbmRvIG9zIGZvcm1hdG9zIMOhdWRpbyBvdSB2w61kZW8uCgpWb2PDqiBkZWNsYXJhIHF1ZSBjb25oZWNlIGEgcG9sw610aWNhIGRlIGNvcHlyaWdodCBkYSBlZGl0b3JhIGRvIHNldSBkb2N1bWVudG8gZSBxdWUgY29uaGVjZSBlIGFjZWl0YSBhcyBEaXJldHJpemVzIGRvIFJJLVVGTUcuCgpWb2PDqiBjb25jb3JkYSBxdWUgbyBSZXBvc2l0w7NyaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIHBvZGUsIHNlbSBhbHRlcmFyIG8gY29udGXDumRvLCB0cmFuc3BvciBhIHN1YSBwdWJsaWNhw6fDo28gcGFyYSBxdWFscXVlciBtZWlvIG91IGZvcm1hdG8gcGFyYSBmaW5zIGRlIHByZXNlcnZhw6fDo28uCgpWb2PDqiB0YW1iw6ltIGNvbmNvcmRhIHF1ZSBvIFJlcG9zaXTDs3JpbyBJbnN0aXR1Y2lvbmFsIGRhIFVGTUcgcG9kZSBtYW50ZXIgbWFpcyBkZSB1bWEgY8OzcGlhIGRlIHN1YSBwdWJsaWNhw6fDo28gcGFyYSBmaW5zIGRlIHNlZ3VyYW7Dp2EsIGJhY2stdXAgZSBwcmVzZXJ2YcOnw6NvLgoKVm9jw6ogZGVjbGFyYSBxdWUgYSBzdWEgcHVibGljYcOnw6NvIMOpIG9yaWdpbmFsIGUgcXVlIHZvY8OqIHRlbSBvIHBvZGVyIGRlIGNvbmNlZGVyIG9zIGRpcmVpdG9zIGNvbnRpZG9zIG5lc3RhIGxpY2Vuw6dhLiBWb2PDqiB0YW1iw6ltIGRlY2xhcmEgcXVlIG8gZGVww7NzaXRvIGRlIHN1YSBwdWJsaWNhw6fDo28gbsOjbywgcXVlIHNlamEgZGUgc2V1IGNvbmhlY2ltZW50bywgaW5mcmluZ2UgZGlyZWl0b3MgYXV0b3JhaXMgZGUgbmluZ3XDqW0uCgpDYXNvIGEgc3VhIHB1YmxpY2HDp8OjbyBjb250ZW5oYSBtYXRlcmlhbCBxdWUgdm9jw6ogbsOjbyBwb3NzdWkgYSB0aXR1bGFyaWRhZGUgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCB2b2PDqiBkZWNsYXJhIHF1ZSBvYnRldmUgYSBwZXJtaXNzw6NvIGlycmVzdHJpdGEgZG8gZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIHBhcmEgY29uY2VkZXIgYW8gUmVwb3NpdMOzcmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBvcyBkaXJlaXRvcyBhcHJlc2VudGFkb3MgbmVzdGEgbGljZW7Dp2EsIGUgcXVlIGVzc2UgbWF0ZXJpYWwgZGUgcHJvcHJpZWRhZGUgZGUgdGVyY2Vpcm9zIGVzdMOhIGNsYXJhbWVudGUgaWRlbnRpZmljYWRvIGUgcmVjb25oZWNpZG8gbm8gdGV4dG8gb3Ugbm8gY29udGXDumRvIGRhIHB1YmxpY2HDp8OjbyBvcmEgZGVwb3NpdGFkYS4KCkNBU08gQSBQVUJMSUNBw4fDg08gT1JBIERFUE9TSVRBREEgVEVOSEEgU0lETyBSRVNVTFRBRE8gREUgVU0gUEFUUk9Dw41OSU8gT1UgQVBPSU8gREUgVU1BIEFHw4pOQ0lBIERFIEZPTUVOVE8gT1UgT1VUUk8gT1JHQU5JU01PLCBWT0PDiiBERUNMQVJBIFFVRSBSRVNQRUlUT1UgVE9ET1MgRSBRVUFJU1FVRVIgRElSRUlUT1MgREUgUkVWSVPDg08gQ09NTyBUQU1Cw4lNIEFTIERFTUFJUyBPQlJJR0HDh8OVRVMgRVhJR0lEQVMgUE9SIENPTlRSQVRPIE9VIEFDT1JETy4KCk8gUmVwb3NpdMOzcmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBzZSBjb21wcm9tZXRlIGEgaWRlbnRpZmljYXIgY2xhcmFtZW50ZSBvIHNldSBub21lKHMpIG91IG8ocykgbm9tZXMocykgZG8ocykgZGV0ZW50b3IoZXMpIGRvcyBkaXJlaXRvcyBhdXRvcmFpcyBkYSBwdWJsaWNhw6fDo28sIGUgbsOjbyBmYXLDoSBxdWFscXVlciBhbHRlcmHDp8OjbywgYWzDqW0gZGFxdWVsYXMgY29uY2VkaWRhcyBwb3IgZXN0YSBsaWNlbsOnYS4KRepositório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2024-02-27T16:17:31Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
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