Efeitos do exercício resistido e do transplante de células tronco mesenquimais em camundongos transgênicos para a doença de Alzheimer

• Ano de defesa: 2019
• Autor(a) principal: Hashiguchi, Debora [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Alzheimer's Disease; Resistance Exercise; Mesenchymal Stem Cell; Amyloid Beta; Inflammation; Doença De Alzheimer; Exercício De Resistência; Transplante De Células Tronco Mesenquimais; Placas Beta Amilóide; Peptídeo Beta Amilóide
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=8000522; https://repositorio.unifesp.br/handle/11600/59900

Objective: In the present study, we analyzed the effects of the resistance exercise (RE) program or the bone-marrow mesenchymal stem cells (MSC) intra-hippocampal transplantation in the locomotor behavior, as well as amyloid load and inflammatory responses, in the hippocampus of mice model of Alzheimer’s disease (AD). Methods: Double transgenic APP/PS1, 6-7 month-old, male mice were used as Alzheimer's disease model, and the respective wild type (WT) littermates as controls. The animals were divided into six groups: WT; WT submitted to RE (WT+RE); WT submitted to MSC transplantation (WT+MSC); APP/PS1 group; APP/PS1 submitted to exercise program (APP/PS1+RE); and APP/PS1 submitted to transplantation (APP/PS1+MSC). The RE groups (WT+RE and APP/PS1+RE) performed 5 weeks of RE program. To the MSC transplantation, the MSC were extracted from C57BL/6- eGFP+ transgenic mice at 4/6 weeks old. The cells were maintained in culture until 7- 10th passage, when they were transplanted in the MSC groups (WT+MSC and APP/PS1+MSC). At the age of 7-8 months old, with the end of the RE program or 5 weeks after the transplantation, the animals performed the Open Filed Task and then were euthanized for the processing of the brain tissues by immunohisochemistry for 6E10 and Iba-1 markers and the hippocampus was analyzed by stereology. Fresh hippocampus samples were collected from the decapitated animals to quantify the expression of Aβ1-42 peptide by ELISA essay and IL-1α, IL-4, IL-6, IL-10 by MilliplexMAP analysis. Results: APP/PS1 mice presented hyper locomotion, Aβ plaques formation and higher levels of IL-1α, IL-6, IL-4 cytokines. APP/PS1+RE group maintained the locomotion behavior to WT group levels; presented decreased Aβ plaques; increased microglia recruitment compared to WT+RE group; and reduced levels of pro-inflammatory cytokines, near WT group. After 6 weeks of treatment, APP/PS1+MSC group presented increased microglia recruitment, but there are no treatment effect in locomotion, Aβ load or cytokine levels. Conclusions: Our study indicates that RE shows beneficial effects on the behavior, amyloid burden and inflammation presented in AD and therefore has therapeutic potential for the improvement of AD neuropathology. After 6 weeks, the MSC transplantation presented no differences other than microglial recruitment. According to our results RE was shown to be a more effective treatment for AD-related behavioral, amyloid- xi loading and inflammatory changes compared to the intra-hipocampal MSC transplantation.