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Trace amounts of copper induce neurotoxicity in the cholesterol-fed mice through apoptosis.

Lu J, Zheng YL, Wu DM, Sun DX, Shan Q, Fan SH

Institute of Molecular Medicine and Genetics Research Center, School of Basic Medical Science, Southeast University, Nanjing 210009, PR China.

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.

Published 4 December 2006 in FEBS Lett, 580(28): 6730-40.
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