Increased extracellular levels of glutamate in the hippocampus of chronically epileptic rats.

Abstract

An increase in the release of excitatory amino acids has consistently been observed in the hippocampus during seizures, both in humans and animals. However, very little or nothing is known about the extracellular levels of glutamate and aspartate during epileptogenesis and in the interictal chronic period of established epilepsy. The aim of this study was to systematically evaluate the relationship between seizure activity and changes in hippocampal glutamate and aspartate extracellular levels under basal and high K(+)-evoked conditions, at various time-points in the natural history of experimental temporal lobe epilepsy, using in vivo microdialysis. Hippocampal extracellular glutamate and aspartate levels were evaluated: 24h after pilocarpine-induced status epilepticus (SE); during the latency period preceding spontaneous seizures; immediately after the first spontaneous seizure; in the chronic (epileptic) period. We found that (i) basal (spontaneous) glutamate outflow is increased in the interictal phases of the chronic period, whereas basal aspartate outflow remains stable for the entire course of the disease; (ii) high K(+) perfusion increased glutamate and aspartate outflow in both control and pilocarpine-treated animals, and the overflow of glutamate was clearly increased in the chronic group. Our data suggest that the glutamatergic signaling is preserved and even potentiated in the hippocampus of epileptic rats, and thus may favor the occurrence of spontaneous recurrent seizures. Together with an impairment of GABA signaling (Soukupova et al., 2014), these data suggest that a shift toward excitation occurs in the excitation/inhibition balance in the chronic epileptic state.

• Authors: M Soukupova, A Binaschi, C Falcicchia, E Palma, P Roncon, S Zucchini, M Simonato
• Journal: Neuroscience (Neuroscience) Vol. 301 Pg. 246-53 (Aug 20 2015) ISSN: 1873-7544 [Electronic] United States
• PMID: 26073699 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Muscarinic Agonists
• Pilocarpine
• Glutamic Acid
• gamma-Aminobutyric Acid
• Scopolamine

Topics

• Animals
• Chromatography, High Pressure Liquid (methods)
• Chronic Disease
• Disease Models, Animal
• Electroencephalography
• Epilepsy (chemically induced, pathology)
• Extracellular Fluid (drug effects, metabolism)
• Glutamic Acid (metabolism)
• Hippocampus (cytology, metabolism)
• Male
• Microdialysis
• Muscarinic Agonists (toxicity)
• Pilocarpine (toxicity)
• Rats
• Rats, Sprague-Dawley
• Scopolamine (toxicity)
• Signal Transduction (drug effects)
• gamma-Aminobutyric Acid (metabolism)