Efeito neuroprotetor do antagonismo dos receptores do tipo P2X7 no Parkinsonismo experimental induzido por rotenona em ratos

Abstract

Parkinson's Disease (PD) is characterized by the progressive loss of dopaminergic neurons from the substantia nigra, leading to severe reduction in dopamine levels associated with neuroinflammation, resulting in various motor and non-motor symptoms. Rotenone (ROT) is an insecticide used in gardening that mimics the symptoms and pathophysiology of PD. Activation of P2X7 receptors by ATP plays an important role in several inflammatory processes. Thus, the present study aimed to investigate the antagonistic effects of P2X7 receptors by Brilliant Blue G (BBG) on motor and non-motor deficits and neuronal damage induced by ROT in rats. 80 Wistar rats were divided into 4 groups: CTL (ROT vehicle: 2% DMSO in sunflower oil, ip, 21 days) and BBG vehicle, (ip, 15 days), BBG CTL (ROT vehicle, ip, 21 days and BBG 50 mg / kg ip, 15 days), ROT (ROT 2.75 mg / kg, ip for 21 days and BBG vehicle) and BBG (ROT 2.75 mg / kg, ip, 21 days and BBG 50 mg / kg ip, 15 days). The animals were submitted to tests to evaluate the motor and non-motor deficits, at the end of the protocol the animals were euthanized to perform dopamine analysis, by HPLC and immunohistopathological evaluation (TH, GFAP and Iba-1). The results showed that the rotenone-induced deficit in the detection of volatile odors after 7 days of administration can be used as a starting point for treatment, and BBG protects the rotenone-induced deficit in horizontal and vertical exploration and mean velocity in the test of In the open field, an improvement in motor coordination deficit in the rotarod test and prevention of anhedonia in the sucrose preference test was also observed and protected against working memory impairment in the Y-maze test. BBG also protected exposed animals to rotenone from dopaminergic neurodegeneration (TH) and prevented from microgliosis (Iba-1). These results showed that the blockade of P2X7 receptors by BBG can prevent motor and non-motor deficits present in PD by controlling neurodegeneration and microgliosis.