Effects of Kainic Acid on High-Energy Metabolites in the Mouse Striatum |
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Authors: | Konrad C Retz Joseph T Coyle |
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Institution: | Departments of Neuroscience, Pharmacology and Experimental Therapeutics, and Psychiatry and the Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland, U.S.A. |
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Abstract: | Abstract: Intrastriatal injection of either kainic acid (0.35 μg) or ibotenic acid (7.0 μg) in the mouse causes a profound and selective degeneration of striatal neurons accompanied by a secondary astrocytic response. The kainate injection (0.35 μg) resulted in significant decrements in the striatal levels of phosphocreatine and ATP by 30 min, a progressive reduction in adenosine phosphates between 30 min and 48 h, and a decrease in energy charge; whereas lactate levels increased by 44% at 2 h, glucose levels fell by 56%. Two hours after intrastriatal injection of ibotenic acid (7.0 μg) similar alternations in striatal high-energy phosphates and glucose disposition were found. Prior decortication protected against the neurotoxic effects of kainate in the mouse striatum and prevented the alterations in high-energy phosphates at 2 h although lactate levels increased by 212%. These findings in vivo are consistent with the hypothesis that the neurotoxic effects of acidic excitatory amino acids involve a profound activation of energy consumption by affected neurons. |
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Keywords: | Excitotoxins Energy metabolism Ibotenic acid Kainic acid Striatum |
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