Efeito protetor de 7-cloro-4-(fenilselanil) quinolina no déficit de memória e na ansiedade em um modelo de doença de Alzheimer: envolvimento do efeito antioxidante e anticolinesterásico

Abstract

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder that occurs predominantly in adulthood; characterized by an insidious onset, slow deterioration in cognition, and loss of memory, functional capacity, behavior, and mood. The available treatments are only symptomatic, improve some cognitive and functional aspects, but are not able to prevent the progression of the disease. Therefore, the search for new treatments capable of protecting/treating AD has intensified. This study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on memory and anxiety impairment in an β-amyloid peptide (βa)-induced DA model in mice. In addition, the involvement of acetylcholinesterase activity (AChE) and lipid peroxidation in the hippocampus and cerebral cortex of mice were evaluated. Swiss male mice were pretreated with 4-PSQ (1 mg/kg, intragastric (i.g.), daily) for fourteen days. Thirty minutes after the first treatment with 4-PSQ, the animals received a single injection of βa (3 nmol/3 μl/per site, intracerebroventricular (i.c.v.)). Mice were submitted to behavioral tasks (open field, elevated plus maze, Barnes maze, recognition and localization of objects and inhibitory avoidance tests) from the fifth day of the experimental protocol. On day 15, animals were anesthetized and blood was collected for biochemical markers (glucose, triglycerides, urea, cholesterol, aspartate (AST) and alanine (ALT) aminotransferases) and the cerebral cortex and hippocampus were removed for determination of AChE activity and thiobarbituric acid reactive species (TBARS) levels. The βa peptide caused memory impairment, an anxiogenic behavior, an increase in AChE activity, and an increase in TBARS levels in the cerebral cortex and hippocampus as well as in plasma cholesterol levels. 4-PSQ protected against behavioral changes, AChE activity, TBARS levels, and plasma cholesterol levels. In conclusion, 4-PSQ protected against impairment in learning and memory as well as anxiety in a model of AD induced by βa in mice. In addition, the anti-cholinesterase action, antioxidant effect and cholesterol metabolism are involved in the pharmacological effect of this compound.