The toxic influence of paraquat on hippocampus of mice: involvement of oxidative stress

Abstract

Environmental paraquat (PQ) exposure has been suggested to be a potential risk factor for neurodegenerative disorders such as Parkinson's disease (PD). The hippocampus plays an important role in the learning and memory abilities of the brain. This study aims to demonstrate the effect and mechanism of paraquat toxicity on the hippocampus of mice. Kunming mice were randomly divided into four groups (one control and three treatment groups) and the dosage levels were defined as 0, 0.89, 2.67 and 8mg/kg body weight. Paraquat was given orally, once a day and for 28 consecutive days. After treatment with paraquat, the hippocampus cells were found to be irregular and the cytoplasm was found to be condensed. The nissl bodies were reduced and apoptotic or necrotic neuron was observed. Morris water maze tests showed that the response latency increased significantly in animals that were administered paraquat. The level of malondialdehyde (MDA) and generation of reactive oxygen species (ROS) in the hippocampus of mice increased significantly. The activities of total superoxide dismutase (SOD) in the hippocampus of mice decreased significantly after treatment with paraquat. An analysis of the energy metabolism of hippocampus showed that the concentration of adenosine-triphosphate (ATP) decreased significantly in the hippocampus after treatment with paraquat, which implied that the energy synthesis of mitochondria with hippocampal neurocytes declined. The level of 8-OHdG in mitochondrial DNA (mtDNA) increased significantly after treatment with paraquat, which indicated that the oxidative damage of mtDNA increased. This suggests that paraquat had a toxic influence on the hippocampus of mice, and that the mechanism of toxicity might be associated with the mitochondrial injury of hippocampal neurocytes induced by oxidative stress.