Kainic acid-mediated excitotoxicity as a model for neurodegeneration |
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Authors: | Qun Wang Sue Yu Agnes Simonyi Grace Y Sun Albert Y Sun |
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Institution: | (1) Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO;(2) Department of Biochemistry, University of Missouri School of Medicine, Columbia, MO |
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Abstract: | Neuronal excitation involving the excitatory glutamate receptors is recognized as an important underlying mechanism in neurodegenerative
disorders. Excitation resulting from stimulation of the ionotropic glutamate receptors is known to cause the increase in intracellular
calcium and trigger calcium-dependent pathways that lead to neuronal apoptosis. Kainic acid (KA) is an agonist for a subtype
of ionotropic glutamate receptor, and administration of KA has been shown to increase production of reactive oxygen species,
mitochondrial dysfunction, and apoptosis in neurons in many regions of the brain, particularly in the hippocampal subregions
of CA1 and CA3, and in the hilus of dentate gyrus (DG). Systemic injection of KA to rats also results in activation of glial
cells and inflammatory responses typically found in neurodegenerative diseases. KA-induced selective vulnerability in the
hippocampal neurons is related to the distribution and selective susceptibility of the AMPA/kainate receptors in the brain.
Recent studies have demonstrated ability of KA to alter a number of intracellular activities, including accumulation of lipofuscin-like
substances, induction of complement proteins, processing of amyloid precursor protein, and alteration of tau protein expression.
These studies suggest that KA-induced excitotoxicity can be used as a model for elucidating mechanisms underlying oxidative
stress and inflammation in neurodegenerative diseases. The focus of this review is to summarize studies demonstrating KA-induced
excitotoxicity in the central nervous system and possible intervention by anti-oxidants. |
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Keywords: | Kainic acid excitotoxicity oxidative stress neuronal death astrocyte microglia selective vulnerability hippocampal neurodegeneration resveratrol antioxidant |
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