Dopamine-induced oxidative stress in neurons with glutathione deficit: implication for schizophrenia.

Details

Serval ID
serval:BIB_E80C13ACAAE4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dopamine-induced oxidative stress in neurons with glutathione deficit: implication for schizophrenia.
Journal
Schizophrenia Research
Author(s)
Grima G., Benz B., Parpura V., Cuénod M., Do K.Q.
ISSN
0920-9964
Publication state
Published
Issued date
2003
Peer-reviewed
Oui
Volume
62
Number
3
Pages
213-224
Language
english
Abstract
Glutathione (GSH) is the main non-protein antioxidant and plays a critical role in protecting cells from damage by reactive oxygen species (ROS) generated by dopamine (DA) metabolism. We reported a decrease of GSH levels ([GSH]) in CSF and in prefrontal cortex in vivo in schizophrenics [Eur. J. Neurosci. 12 (2000) 3721]. A GSH deficit may lead to membrane peroxidation and microlesions around dopaminergic terminals, resulting in loss of connectivity. To test this hypothesis, we studied the effect of DA in cultured cortical neurons with low [GSH]. DA alone decreased [GSH] by 40%. This effect appears to result from direct conjugation of DA semiquinone/quinone with GSH. Ethacrynic acid (EA) decreased [GSH] in a concentration-dependent manner. When added to EA, DA further lowers [GSH]. As this additional decrease is blocked by superoxide dismutase (SOD) or D(1)/D(2) receptor antagonists, it likely involves the generation of superoxide via activation of DA receptors. It also reduces the mitochondrial membrane potential. Most interestingly, a significant decrease in number of neuronal processes (spines analogous) was induced by 24-h application of DA only in low [GSH]. These data, compatible with our hypothesis, is consistent with the dendritic spines reduction reported in schizophrenia and could be related to abnormalities in synaptic connectivity.
Keywords
Animals, Dopamine/metabolism, Glutathione/cerebrospinal fluid, Glutathione/deficiency, Mice, Neurons/metabolism, Oxidative Stress/physiology, Receptors, Dopamine/metabolism, Schizophrenia/metabolism, Schizophrenia/physiopathology, Superoxide Dismutase/metabolism, Synaptic Transmission/physiology
Pubmed
Web of science
Create date
10/03/2008 10:49
Last modification date
20/08/2019 16:10
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