Effects of moderate alcohol consumption on Alzheimer's Disease related to central insulin resistance

Abstract

Alzheimer's Disease (AD), the most common form of dementia, is a highly prevalent progressive neurodegenerative disorder. AD's main symptoms are cognitive decline and personality alterations, including memory loss and mental confusion. The main pathophysiological biomarkers of AD are amyloid-beta (A²) plaque and neurofibrillary tangles resultant of tau protein hyperfosforilation. Suggestive findings of alterations in the central regulation of the insulin signaling pathway in AD contributed for authors to consider the disease as the third type of diabetes (T3DM). Although AD still doesn't have a completely defined etiology, studies suggest that lifestyle habits are risk factors that can influence the development of the disease. In that way, alcohol, the world's most consumed licit drug, seems to have neuroprotective effects on the disease when consumed in low or moderate amounts. However, these results are still controversial and the mechanisms responsible for these effects have not yet been elucidated. On the other hand, several studies have shown that low or moderate alcohol consumption is capable of increasing peripheral insulin sensitivity. Thus, considering the important connection between AD and central insulin resistance, the aim of this project is to analyze the possible neuroprotective effects of moderate alcohol consumption on the central regulation of the insulin signaling pathway in AD. For this, 32 male Sprague-Dawley rats will be used, which will undergo intracerebroventricular injection of streptozotocin (STZ) or vehicle. These animals will be treated with 3% Ethanol or vehicle for 4 weeks and then will be submitted to the Barnes Labyrinth (BL) for spatial memory assessment. Subsequently, these rats will be euthanized and their hippocampus will be dissected for quantification of tau, phosphorylated tau, AKT, phosphorylated AKT, GSK-3±/², and phosphorylated GSK-3±/² proteins using the Western Blot protocol. Therefore, our hypothesis is that moderate alcohol consumption has a neuroprotective effect on AD by increasing central insulin sensitivity.(AU)