Redox mechanisms at the glutamate synapse and their significance: a review.
This paper reviews what is currently known about the redox state of the glutamate synapse and its possible role in modulating synaptic plasticity and thus learning and neurocomputation. The hypothesis is presented that the growth or pruning of the synaptic spine is controlled in part by the balance in the synapse between neurodestructive pro-oxidants (e.g., nitric acid radical and hydrogen peroxide) and neuroprotective antioxidants (e.g., ascorbate and carnosine). In addition, there may be a role for catecholamines, in particular dopamine, related to its role in reinforcement signalling. Activation of the dopamine D2 receptor induces the synthesis of an antioxidant enzyme, possibly catalase. Dopamine may also affect the redox balance in the glutamate synapse directly by diffusion from the adjacent dopaminergic bouton-en-passage. Catecholamines are powerful antioxidants, scavengers of free radicals and iron chelators. Catecholamine-iron complexes are potent dismuters of superoxide ions. Additional agents participating in spine pruning may be neurotoxic catecholamine o-quinones present in the brain. This system may be at fault in schizophrenia and Parkinson's disease. Experiments to test the hypothesis are suggested.
D000975:Antioxidants / Q000378:metabolism; D004298:Dopamine / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism* / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000502:physiology