Efeito do selenofuranosídeo sobre modelos de doença de Alzheimer em camundongos

Abstract

World population is increasingly older and neurodegenerative diseases, such as Alzheimer’s disease (AD), are becoming more common. New ways to retard AD progress are being studied, such as substances with antioxidant and anti-inflammatory properties, like organoselenium compounds. The aim of this study was to evaluate the effect of selenofuranoside, a synthetic organoselenium compound, in two Alzheimer-like sporadic dementia animal model. First experiment – Single administration of Aβ peptide (fragment 25–35; 3 nmol/3 μL) or distilled water were administered via intracerebroventricular (i.c.v.) in male mice. Selenofuranoside (5 mg/kg, SE) or vehicle (canola oil, VEH) was administered via oral 30 min before Aβ and for 7 subsequent days. Memory was tested through Morris water maze (MWM) and step-down passive avoidance (SDPA) tests. Oxidative stress balance was assessed via SOD, CAT, GPx, GR and GST activities along with reactive species (RS) and GSH levels. Inflammatory cytokines levels were measured to assess inflammation progress, and AChE activity to estimate synaptic status. Aβ group presented a significant decrease in SOD activity and an increase in AChE activity, RS levels, IL-6 and GSH. A reduction in step-down latency in SDPA, and also latency to reach the platform former location in MWM was observed. SE was able to protect against memory loss in mice, probably due to AChE activity modulation. The compound was also able to protect against SOD activity reduction, reducing RS levels. Although an increase in IL-6 was observed in SE group, Aβ+SE showed the same levels of control group. Second experiment – male and female wild-type (WT) mice (C57BL/6J) and APP/PS1 transgenic (TG) mice were used. SE (10 mg/kg, SE) or VEH were administered via oral twice a week, for 5 month-period. Behavioural tests including Morris water maze (MWM), Y-Maze, elevated plus-maze (EPM), Social Preference/Social Novelty test (SPSN), were performed to assess memory and anxiety-like behavior. Both genotypes performed alike at Y-maze, EPM and SPSN tests. At MWM acquisition phase, a main-effect of genotype was observed at days 7, 9 and 10, where TG mice presented an increase in path length and latency to find the platform. Also, WT mice spent more time in the target quadrant during the second probe of MWM. Immunohistochemical analysis was done in coronal brain sections to evaluate Aβ deposits, GFAP production and amyloid plaques. SE treatment significantly decreased GFAP production and Aβ1-16 deposits at TG mice, but this was not reflected at the behavioral tests. Nonetheless, the fact that selenofuranoside was able to reduce Aβ1-16 deposits in APP/PS1 mice and protected against various alterations exhibited by Aβ fragment is promising for further studies.