Perfil inflamatório em modelo experimental da Doença de Alzheimer com dieta acrescida de colesterol

• Ano de defesa: 2024
• Autor(a) principal: Érica Paulino Silva
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - DEPARTAMENTO DE FARMACOLOGIA; Programa de Pós-Graduação em Neurociências; UFMG
• Palavras-chave em Português: Doença de Alzheimer; Colesterol; Citocinas; Neurociências
• Link de acesso: http://hdl.handle.net/1843/77722

Alzheimer's disease (AD) stands as the foremost etiology of dementia, characterized by a progressive deterioration in memory, cognitive functions, accompanied by behavioral alterations and functional debilitation. The intricate interplay of neuroinflammatory cascades assumes a pivotal role in instigating and perpetuating the pathological trajectory of AD, orchestrated by a myriad of factors. While the precise mechanistic underpinnings remain elusive, mounting evidence underscores a putative pathological nexus linking cholesterol dysregulation with AD. This study endeavors to scrutinize the impact of heightened cholesterol intake on inflammatory indices within an animal model of AD. Male and female mice harboring the APP/PS1 double- transgenic genotype were utilized to model AD, juxtaposed against WT littermates as controls. Commencing at 6 months of age, subjects were subjected to either a standard diet or an equicaloric diet supplemented with 1.25% cholesterol for a duration of eighteen weeks. Upon completion of the dietary intervention, animals were euthanized, and specimens encompassing the kidneys, spleen, prefrontal cortex, cortex, hippocampus, and striatum were procured. Inflammatory mediators were assessed utilizing Cytometric Bead Array (CBA) for a panel of cytokines comprising IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17, and TNF-α. Our findings unveil a notable discrepancy in TNF- α concentrations within splenic samples, manifesting a higher abundance in the control cohort compared to the APP/PS1 group following cholesterol supplementation. However, discernible disparities in inflammatory parameters across genotypes and dietary regimens were not evident in other sampled organs. Collectively, these observations delineate that the incorporation of 1.25% cholesterol fails to elicit discernible alterations in the inflammatory milieu within the prefrontal cortex, cortex, hippocampus, and striatum. Conversely, a discernible reduction in TNF-α levels within the spleen of AD-afflicted animals underscores a potential modulatory role of cholesterol in peripheral inflammatory responses in the context of AD pathogenesis. Hence, our findings underscore the imperative for further elucidating the intricate interplay between cholesterol metabolism and neuroinflammation in the context of AD.