Authors: Yu Deng Congcong Jiao Chao Mi Bin Xu Yuehui Li Fei Wang Wei Liu Zhaofa Xu
Publish Date: 2014/06/28
Volume: 51, Issue: 1, Pages: 68-88
Abstract
Excessive manganese Mn induces oxidative stress and dopaminergic neurodegeneration However the relationship between them during Mn neurotoxicity has not been clarified The purpose of this study was to investigate the probable role of melatonin MLT against Mninduced motor dysfunction and neuronal loss as a result of antagonizing oxidative stress and dopaminergic neurodegeneration Mice were randomly divided into five groups as follows control MnCl2 low MLT + MnCl2 median MLT + MnCl2 and high MLT + MnCl2 Administration of MnCl2 50 mg/kg for 2 weeks significantly induced hypokinesis dopaminergic neurons degeneration and loss neuronal ultrastructural damage and apoptosis in the substantia nigra and the striatum These conditions were caused in part by the overproduction of reactive oxygen species malondialdehyde accumulation and dysfunction of the nonenzymatic GSH and enzymatic GSHPx superoxide dismutase quinone oxidoreductase 1 glutathione Stransferase and glutathione reductase antioxidative defense systems Mninduced neuron degeneration astrocytes and microglia activation contribute to the changes of oxidative stress markers Dopamine DA depletion and downregulation of DA transporter and receptors were also found after Mn administration this might also trigger motor dysfunction and neurons loss Pretreatment with MLT prevented Mninduced oxidative stress and dopaminergic neurodegeneration and inhibited the interaction between them As a result pretreatment with MLT significantly alleviated Mninduced motor dysfunction and neuronal loss In conclusion Mn treatment resulted in motor dysfunction and neuronal loss possibly involving an interaction between oxidative stress and dopaminergic neurodegeneration in the substantia nigra and the striatum Pretreatment with MLT attenuated Mninduced neurotoxicity by means of its antioxidant properties and promotion of the DA system
Keywords: