| Resumo: | Alzheimer’s disease is the commonest form of dementia worldwide. Clinically, this neurodegenerative disorder is characterized by cognitive decline, changes in personality and mood, and disorientation. Neuropathologically, it is characterized by the extracellular accumulation of beta-amyloid peptide (Aβ) forming senile plaques, and the intracellular deposition of hyperphosphorylated Tau protein forming neurofibrillary tangles. Alzheimer’s disease affects primarily the hippocampus and may progress towards the cerebral cortex. Recent studies showed that deregulation of histone acetylation is associated with increased chromatin compaction and the subsequent decrease in gene transcription. Thus, the study of inhibitors of enzymes that promote histone deacetylation, HDACs (Histone DeACetylases) became a matter of interest in Alzheimer’s disease therapeutics. Besides, it was shown that Aβ peptide induces the production of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), that further promote the activity of the Nrf2 (nuclear factor erythroid 2-related factor 2) transcription factor, altering cellular/tissue antioxidant profile. In this perspective, in this study we aimed to evaluate the possible effect of a HDAC inhibitor, sodium butyrate (SB) (1 mg/kg/day, for 42 days), in the attenuation of Alzheimer’s disease-related symptoms and neuropathology, using the triple transgenic mice for Alzheimer’s disease (3xTg-AD). 3xTg-AD mice at 10.5 months of age showed increased anxiety levels associated to the disease in comparison to non-transgenic/wild-type (WT) mice, that was not reverted by treatment with SB. Memory processes analysed through the Y-maze, the novel object recognition and object displacement tests showed no alterations in 3xTg-AD animals nor after treatment with SB. Quantification of acetylation levels of histone H3, the levels of total and phosphorylated Tau, as well as Nrf2 levels showed no significant differences between control and 3xTg-AD animals either. Treatment of 3xTg-AD mice with SB did not significantly affect any of these parameters either. Aiming to explain the lack of behavioural and biochemical differences between the 3xTg-AD and WT animals, the presence of Aβ aggregates and hyperphosphorylated Tau were assessed by immunohistochemistry in the hippocampus of 3xTg-AD mice. However, we did not observe any histopathological markers associated with this neurodegenerative disorder. The most probable explanation for these results is a delay in the disease development, leading to a later appearance of brain histopathological markers and behavioural alterations, as suggested by recent literature. In future studies, it will be interesting to analyse an animal model with a more severe pathological progression, such as the APP/PS1 transgenic mice.
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