Transient Inhibition of Glutamate Uptake In Vivo Induces Neurodegeneration when Energy Metabolism Is Impaired

Transient Inhibition of Glutamate Uptake In Vivo Induces Neurodegeneration when Energy Metabolism... Abstract : Impairment of glutamate transport during ischemia might be related to the elevation of the extracellular concentration of glutamate and ischemic neuronal damage. Additionally, impairment of energy metabolism in vivo leads to neurodegeneration apparently mediated by a secondary excitotoxic mechanism. In vitro observations show that glucose deprivation and inhibition of energy metabolism exacerbate the toxic effects of glutamate. We have previously shown that glutamate uptake inhibition in vivo by l‐trans‐pyrrolidine‐2,4‐dicarboxylate (PDC) leads to a substantial elevation in the extracellular concentration of excitatory amino acids that is not associated with cell death. These observations suggest that energy depletion during ischemia might be determinant of ischemic neuronal damage. To investigate whether impairment of energy metabolism in vivo increases neuronal susceptibility to glutamate uptake inhibition, we studied the effect of glutamate accumulation induced by the intrahippocampal or intrastriatal administration of PDC in energy‐deficient rats chronically treated with 3‐nitropropionic acid (3‐NP), which irreversibly inhibits the tricarboxylic acid cycle and electron transport chain. Extracellular glutamate levels were monitored by HPLC from fractions collected from microdialysis probes, and neuronal damage was evaluated by histological analysis. Our results show that glutamate uptake inhibition leads to marked neuronal damage in energy‐deficient rats but not in intact animals, which apparently is not related to an additional elevation of glutamate levels induced by 3‐NP. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Transient Inhibition of Glutamate Uptake In Vivo Induces Neurodegeneration when Energy Metabolism Is Impaired

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
© International Society for Neurochemistry
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1046/j.1471-4159.1999.0720129.x
Publisher site
See Article on Publisher Site

Abstract

Abstract : Impairment of glutamate transport during ischemia might be related to the elevation of the extracellular concentration of glutamate and ischemic neuronal damage. Additionally, impairment of energy metabolism in vivo leads to neurodegeneration apparently mediated by a secondary excitotoxic mechanism. In vitro observations show that glucose deprivation and inhibition of energy metabolism exacerbate the toxic effects of glutamate. We have previously shown that glutamate uptake inhibition in vivo by l‐trans‐pyrrolidine‐2,4‐dicarboxylate (PDC) leads to a substantial elevation in the extracellular concentration of excitatory amino acids that is not associated with cell death. These observations suggest that energy depletion during ischemia might be determinant of ischemic neuronal damage. To investigate whether impairment of energy metabolism in vivo increases neuronal susceptibility to glutamate uptake inhibition, we studied the effect of glutamate accumulation induced by the intrahippocampal or intrastriatal administration of PDC in energy‐deficient rats chronically treated with 3‐nitropropionic acid (3‐NP), which irreversibly inhibits the tricarboxylic acid cycle and electron transport chain. Extracellular glutamate levels were monitored by HPLC from fractions collected from microdialysis probes, and neuronal damage was evaluated by histological analysis. Our results show that glutamate uptake inhibition leads to marked neuronal damage in energy‐deficient rats but not in intact animals, which apparently is not related to an additional elevation of glutamate levels induced by 3‐NP.

Journal

Journal of NeurochemistryWiley

Published: Jan 1, 1999

Keywords: ; ; ;

References

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