title: Melatonin inhibits manganese-induced motor dysfunction and neuronal loss in mice: involvement of oxidative stress and dopaminergic neurodegeneration.
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 Mn-induced 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 (GSH-Px, superoxide dismutase, quinone oxidoreductase 1, glutathione S-transferase, and glutathione reductase) antioxidative defense systems. Mn-induced 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 Mn-induced oxidative stress and dopaminergic neurodegeneration and inhibited the interaction between them. As a result, pretreatment with MLT significantly alleviated Mn-induced 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 Mn-induced neurotoxicity by means of its antioxidant properties and promotion of the DA system.
authors: Department of Environmental Health, School of Public Health, China Medical University, North 2nd Road 92, Heping ward, Shenyang, Liaoning, 110001, People's Republic of China, dengyu.cmu@163.com.
authors: Yu
authors: Y
authors: Deng
authors: Congcong
authors: C
authors: Jiao
authors: Chao
authors: C
authors: Mi
authors: Bin
authors: B
authors: Xu
authors: Yuehui
authors: Y
authors: Li
authors: Fei
authors: F
authors: Wang
authors: Wei
authors: W
authors: Liu
authors: Zhaofa
authors: Z
authors: Xu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D039481:CD11b Antigen / Q000378:metabolism; D002712:Chlorides / Q000009:adverse effects*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017895:Manganese Compounds / Q000009:adverse effects*; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009068:Movement / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D039481:CD11b Antigen; D002712:Chlorides; D050483:Dopamine Plasma Membrane Transport Proteins; D005904:Glial Fibrillary Acidic Protein; D017895:Manganese Compounds; D017382:Reactive Oxygen Species; D011954:Receptors, Dopamine; D008315:Malondialdehyde; D014446:Tyrosine 3-Monooxygenase; D010751:Phosphopyruvate Hydratase; D005978:Glutathione; D008550:Melatonin; C025340:manganese chloride; D004298:Dopamine