title: Intrastriatal manganese chloride exposure causes acute locomotor impairment as well as partial activation of substantia nigra GABAergic neurons.
abstract: Our previous studies showed chronic exposure to manganese chloride (Mn) causes locomotor impairment and lesion of dopaminergic neurons in substantia nigra (SN). But effects of acute Mn exposure on locomotor ability, SN dopaminergic and GABAergic neurons were not clear. In the current study, Mn was injected into the striatum of GAD(67)-GFP mice. Twenty-four hours after injection, locomotor ability was quantitatively evaluated with behavioral tests (rotarod test and open field test). Meanwhile, the numbers of dopaminergic and GABAergic neurons were counted through immunofluorescent staining for TH and GFP respectively, and activations of dopaminergic and GABAergic neurons were evaluated by double immunofluorescent labeling for TH/Fos and GFP/Fos, respectively. Behavioral tests showed a significant locomotor impairment 24h after Mn injection. The numbers of SN dopaminergic and GABAergic neurons were not altered significantly 24h after Mn injection; however, some of SN GABAergic neurons were activated and dopaminergic neurons were left inactivated. In addition, there were still a large number of Mn-activated neurons that fell into neither dopaminergic nor GABAergic criteria. Our data suggested that activation of SN GABAergic neurons but not lesion of dopaminergic neurons, which was found to play an important role in the Mn-induced chronic neurotoxicity in our previous studies, contributed partially to Mn-induced acute locomotor impairment. Therefore we come to the conclusion that Mn exposure can induce acute or chronic neurotoxicity via different neuronal elements.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Yang
authors.forename: Jiaze
authors.initials: J
authors.lastname: An
authors.forename: Yayun
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenjing
authors.initials: W
authors.lastname: Luo
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Mei
authors.forename: Shengxi
authors.initials: S
authors.lastname: Wu
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000187:drug effects; D002712:Chlorides / Q000008:administration & dosage / Q000633:toxicity*; D003342:Corpus Striatum; D004298:Dopamine / Q000502:physiology; D005455:Fluorescent Antibody Technique; D020233:Gait Disorders, Neurologic / Q000139:chemically induced*; D005968:Glutamate Decarboxylase / Q000235:genetics; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D007267:Injections; D008124:Locomotion / Q000187:drug effects; D008297:Male; D017895:Manganese Compounds / Q000008:administration & dosage; D020149:Manganese Poisoning / Q000378:metabolism* / Q000503:physiopathology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D004856:Postural Balance / Q000187:drug effects; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D002712:Chlorides; D017895:Manganese Compounds; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C025340:manganese chloride; D004298:Dopamine