title: Disturbance of aerobic metabolism accompanies neurobehavioral changes induced by nickel in mice.
abstract: The oral ingestion of soluble nickel compounds leads to neurological symptoms in humans. Deficiencies in aerobic metabolism induced by neurotoxic stimulus can cause an energy crisis in the brain that results in a variety of neurotoxic effects. In the present study, we focused on the aerobic metabolic states to investigate whether disturbance of aerobic metabolism was involved in nickel-induced neurological effects in mice. Mice were orally administered nickel chloride, and neurobehavioral performance was evaluated using the Morris water maze and open field tests at different time points. Aerobic metabolic states in the cerebral cortex were analyzed at the same time points at which neurobehavioral changes were evident. We found that nickel exposure caused deficits in both spatial memory and exploring activity in mice and that nickel was deposited in their cerebral cortex. Deficient aerobic metabolism manifested as decreased O2 consumption and ATP concentrations, lactate and NADH accumulation, and oxidative stress. Meanwhile, the activity of prototypical iron-sulfur clusters (ISCs) containing enzymes that are known to control aerobic metabolism, including complex I and aconitase, and the expression of ISC assembly scaffold protein (ISCU) were inhibited following nickel deposition. Overall, these data suggest that aerobic metabolic disturbances, which accompanied the neurobehavioral changes, may participate in nickel-induced neurologic effects. The inactivation of ISC containing metabolic enzymes may result in the disturbance of aerobic metabolism. A better understanding of how nickel impacts the energy metabolic processes may provide insight into the prevention of nickel neurotoxicity.
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Min-Di
authors.initials: MD
authors.lastname: He
authors.forename: Shang-Cheng
authors.initials: SC
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jia-Chuan
authors.initials: JC
authors.lastname: Xiong
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Lu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Zheng-Ping
authors.initials: ZP
authors.lastname: Yu
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000332:Aerobiosis / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D005106:Exploratory Behavior / Q000187:drug effects*; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D009243:NAD / Q000378:metabolism; D009532:Nickel / Q000633:toxicity*; D018384:Oxidative Stress; D010101:Oxygen Consumption / Q000187:drug effects
chemical_list: D007506:Iron-Sulfur Proteins; D009243:NAD; D019344:Lactic Acid; C022838:nickel chloride; D009532:Nickel; D000255:Adenosine Triphosphate; D000154:Aconitate Hydratase
keywords: ATP; Aerobic metabolism; HIF-1α; ISC; ISCU; Iron–sulfur cluster; MDA; MWM; Morris water maze; NAD/NADH; Neurobehavioral change; Nickel; OXPHOS; ROS; SOD; adenosine triphosphate; hypoxia inducible factor-1 alpha; iron–sulfur cluster; iron–sulfur cluster scaffold protein; malondialdehyde; nicotinamide adenine dinucleotide; oxidative phosphorylation; reactive oxygen species; superoxide dismutase