Efeito neuroterapêutico de uma quinolina funcionalizada contendo selênio em modelo de obesidade hipotalâmica em ratos

Abstract

Obesity is considered one of the major global health problems and increases the risk of several medical complications, such as diabetes and mental illnesses. The present study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on obesity parameters, behavioral and neurochemical alterations in hypothalamic obese rats. Male Wistar rats received subcutaneous neonatal injections of monosodium glutamate (MSG, 4g/kg) or saline. After the Lee Index evaluation, rats were divided into groups and treated with 4-PSQ (5 mg/kg, intragastric route) or canola oil once a day (post-natal days – PND 60→76). Open-field, elevated plus maze, forced swimming, object recognition/location memory and step-down inhibitory avoidance tasks were conducted from PND 66 to 74. At PND 76, rats were euthanized and epididymal fat, blood, cerebral cortex, and hippocampus were removed. Blood biochemical parameters and cortical/hippocampal acetylcholinesterase (AChE) and Na+/K+-ATPase activities were assessed. MSG increased Lee Index, characterizing the chemically-induced hypothalamic obesity model. 4-PSQ reverted the increases on the epididymal fat amount, blood glucose and triglyceride levels caused by MSG exposure. 4-PSQ restored anxiety-like and depression-like behaviors induced by neonatal administrations of MSG. Memory deficits found in MSG obese rats were reverted by treatment with 4-PSQ. The neurochemical alterations produced by MSG evidenced by stimulation of Na+/K+-ATPase and AChE activities in the cerebral cortex and hippocampus of rats were restored by 4-PSQ treatment. In summary, 4-PSQ therapy ameliorated hypothalamic obesity-related parameters, as well as psychiatric symptoms, cognitive impairments and neurochemical alterations found in obese rats.