Trace amounts of copper induce neurotoxicity in the cholesterol-fed mice through apoptosis.
Evidence has been gathered to suggest that trace amounts of copper induce neurotoxicity by interaction with elevated cholesterol in diet. Copper treatment alone showed no significant learning and memory impairments in behavioral tasks. However, copper-induced neurotoxicity was significantly increased in mice given elevated-cholesterol diet. Trace amounts of copper decreased the activity of SOD and increased the level of malondialdehyde (MDA) in the brain of cholesterol-fed mouse. Copper also caused an increase in amyloid precursor protein (APP) mRNA level and the activation of caspase-3 in the brain of cholesterol-fed mice. The apoptosis-induced nuclear DNA fragmentation was detected in the brain of those mice by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling staining. These findings suggest that trace amounts of copper induce neurotoxicity in cholesterol-fed mice through apoptosis caused by oxidative stress.
Lu
Jun
J
Institute of Molecular Medicine and Genetics Research Center, School of Basic Medical Science, Southeast University, Nanjing 210009, PR China.
Zheng
Yuan-Lin
YL
Wu
Dong-Mei
DM
Sun
Dong-Xu
DX
Shan
Qun
Q
Fan
Shao-Hua
SH
D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002784:Cholesterol / Q000008:administration & dosage*; D003300:Copper / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007859:Learning Disabilities / Q000139:chemically induced / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning; D008569:Memory Disorders / Q000139:chemically induced / Q000473:pathology; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger; D008315:Malondialdehyde; D003300:Copper; D002784:Cholesterol; D013482:Superoxide Dismutase; D053148:Caspase 3