Autor: |
Cruces-Sande A; Laboratory of Neurochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.; Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain., Garrido-Gil P; Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain.; Laboratory of Cell and Molecular Neurobiology of Parkinson's Disease, Department of Morphological Sciences, Faculty of Medicine, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Institute of Health Carlos III, 28029 Madrid, Spain., Sierra-Paredes G; Laboratory of Neurochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain., Vázquez-Agra N; Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain., Hermida-Ameijeiras Á; Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain., Pose-Reino A; Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain., Méndez-Álvarez E; Laboratory of Neurochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Institute of Health Carlos III, 28029 Madrid, Spain., Soto-Otero R; Laboratory of Neurochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Institute of Health Carlos III, 28029 Madrid, Spain. |
Abstrakt: |
Copper is a trace element whose electronic configuration provides it with essential structural and catalytic functions. However, in excess, both its high protein affinity and redox-catalyzing properties can lead to hazardous consequences. In addition to promoting oxidative stress, copper is gaining interest for its effects on neurotransmission through modulation of GABAergic and glutamatergic receptors and interaction with the dopamine reuptake transporter. The aim of the present study was to investigate the effects of copper overexposure on the levels of dopamine, noradrenaline, and serotonin, or their main metabolites in rat's striatum extracellular fluid. Copper was injected intraperitoneally using our previously developed model, which ensured striatal overconcentration (2 mg CuCl 2 /kg for 30 days). Subsequently, extracellular fluid was collected by microdialysis on days 0, 15, and 30. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and noradrenaline (NA) levels were then determined by HPLC coupled with electrochemical detection. We observed a significant increase in the basal levels of DA and HVA after 15 days of treatment (310% and 351%), which was maintained after 30 days (358% and 402%), with no significant changes in the concentrations of 5-HIAA, DOPAC, and NA. Copper overload led to a marked increase in synaptic DA concentration, which could contribute to the psychoneurological alterations and the increased oxidative toxicity observed in Wilson's disease and other copper dysregulation states. |