Oxaloacetate restores the long-term potentiation impaired in rat hippocampus CA1 region by 2-vessel occlusion

Máté Marosi, János Fuzik, Dávid Nagy, Gabriella Rákos, Zsolt Kis, László Vécsei, József Toldi, Angela Ruban-Matuzani, Vivian I. Teichberg, Tamás Farkas

Research output: Contribution to journalArticlepeer-review

Abstract

Various acute brain pathological conditions are characterized by the presence of elevated glutamate concentrations in the brain interstitial fluids. It has been established that a decrease in the blood glutamate level enhances the brain-to-blood efflux of glutamate, removal of which from the brain may prevent glutamate excitotoxicity and its contribution to the long-lasting neurological deficits seen in stroke. A decrease in blood glutamate level can be achieved by exploiting the glutamate-scavenging properties of the blood-resident enzyme glutamate-oxaloacetate transaminase, which transforms glutamate into 2-ketoglutarate in the presence of the glutamate co-substrate oxaloacetate. The present study had the aim of an evaluation of the effects of the blood glutamate scavenger oxaloacetate on the impaired long-term potentiation (LTP) induced in the 2-vessel occlusion ischaemic model in rat. Transient (30-min) incomplete forebrain ischaemia was produced 72 h before LTP induction. Although the short transient brain hypoperfusion did not induce histologically identifiable injuries in the CA1 region (Fluoro-Jade B, S-100 and cresyl violet), it resulted in an impaired LTP function in the hippocampal CA1 region without damaging the basal synaptic transmission between the Schaffer collaterals and the pyramidal neurons. This impairment could be fended off in a dose-dependent manner by the intravenous administration of oxaloacetate in saline (at doses between 1.5 mmol and 0.1 μmol) immediately after the transient hypoperfusion. Our results suggest that oxaloacetate-mediated blood and brain glutamate scavenging contributes to the restoration of the LTP after its impairment by brain ischaemia.

Original languageEnglish
Pages (from-to)51-57
Number of pages7
JournalEuropean Journal of Pharmacology
Volume604
Issue number1-3
DOIs
StatePublished - 14 Feb 2009
Externally publishedYes

Keywords

  • 2-vessel occlusion
  • Glutamate neurotoxicity
  • Glutamate-scavenging
  • Hypoperfusion
  • LTP
  • Oxaloacetate

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