Disturbance of aerobic metabolism accompanies neurobehavioral changes induced by nickel in mice

• Published in: Neurotoxicology (Park Forest South) Vol. 38; pp. 9 - 16
• Main Authors: He, Min-Di, Xu, Shang-Cheng, Zhang, Xin, Wang, Yan, Xiong, Jia-Chuan, Zhang, Xiao, Lu, Yong-Hui, Zhang, Lei, Yu, Zheng-Ping, Zhou, Zhou
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.09.2013; Elsevier
• Subjects: Aconitate Hydratase - metabolism; Adenosine Triphosphate - metabolism; Aerobic metabolism; Aerobiosis - drug effects; Animals; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Chemical and industrial products toxicology. Toxic occupational diseases; Down-Regulation; Exploratory Behavior - drug effects; Iron-Sulfur Proteins - metabolism; Iron–sulfur cluster; ISCU; Lactic Acid - metabolism; Male; Maze Learning - drug effects; Medical sciences; Metals and various inorganic compounds; Mice; NAD - metabolism; Neurobehavioral change; Nickel; Nickel - toxicity; Oxidative Stress; Oxygen Consumption - drug effects; Toxicology; NAD/NADH; MWM; Neurobehavioral change; Aerobic metabolism; OXPHOS; SOD; HIF-1α; MDA; Iron–sulfur cluster; ROS; ISC; Nickel; ATP; ISCU; Rodentia; Iron―sulfur cluster; Nervous system; Cluster; Transition metal; Iron; Aerobe; Change; Metabolism; Inorganic element; Vertebrata; Mammalia; Mouse; Animal; Behavior; Sulfur; Morris water maze; iron–sulfur cluster scaffold protein; oxidative phosphorylation; nicotinamide adenine dinucleotide; superoxide dismutase; adenosine triphosphate; reactive oxygen species; malondialdehyde; hypoxia inducible factor-1 alpha
• ISSN: 0161-813X; 1872-9711; 1872-9711
• DOI: 10.1016/j.neuro.2013.05.011

•Transient neurobehavioral effects induced by nickel oral exposure.•Nickel deposition in cerebral cortex causes disturbance of aerobic metabolism.•Alteration in iron sulfur cluster scaffold protein may underlie effects of nickel. 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.