title: 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.affiliation: Department of Medical Sciences, Section of Pharmacology, Neuroscience Center, University of Ferrara and National Institute of Neuroscience, Via Fossato di Mortara 17-19, Ferrara, Italy. Electronic address: marie.soukupova@unife.it.
authors.forename: M
authors.initials: M
authors.lastname: Soukupova
authors.affiliation: Department of Medical Sciences, Section of Pharmacology, Neuroscience Center, University of Ferrara and National Institute of Neuroscience, Via Fossato di Mortara 17-19, Ferrara, Italy. Electronic address: anna.binaschi@unife.it.
authors.forename: A
authors.initials: A
authors.lastname: Binaschi
authors.affiliation: Department of Medical Sciences, Section of Pharmacology, Neuroscience Center, University of Ferrara and National Institute of Neuroscience, Via Fossato di Mortara 17-19, Ferrara, Italy. Electronic address: chiara.falcicchia@unife.it.
authors.forename: C
authors.initials: C
authors.lastname: Falcicchia
authors.affiliation: Department of Physiology and Pharmacology, University of Roma "Sapienza", Piazzale Aldo Moro 5, Roma, Italy; IRCCS San Raffaele, Via della Pisana 235, Roma, Italy. Electronic address: eleonora.palma@uniroma1.it.
authors.forename: E
authors.initials: E
authors.lastname: Palma
authors.affiliation: Department of Medical Sciences, Section of Pharmacology, Neuroscience Center, University of Ferrara and National Institute of Neuroscience, Via Fossato di Mortara 17-19, Ferrara, Italy. Electronic address: paolo.roncon@unife.it.
authors.forename: P
authors.initials: P
authors.lastname: Roncon
authors.affiliation: Department of Medical Sciences, Section of Pharmacology, Neuroscience Center, University of Ferrara and National Institute of Neuroscience, Via Fossato di Mortara 17-19, Ferrara, Italy; Laboratory of Technologies for Advanced Therapy (LTTA), Technopole of Ferrara, Via Ludovico Ariosto 35, Ferrara, Italy. Electronic address: silvia.zucchini@unife.it.
authors.forename: S
authors.initials: S
authors.lastname: Zucchini
authors.affiliation: Department of Medical Sciences, Section of Pharmacology, Neuroscience Center, University of Ferrara and National Institute of Neuroscience, Via Fossato di Mortara 17-19, Ferrara, Italy; Laboratory of Technologies for Advanced Therapy (LTTA), Technopole of Ferrara, Via Ludovico Ariosto 35, Ferrara, Italy. Electronic address: michele.simonato@unife.it.
authors.forename: M
authors.initials: M
authors.lastname: Simonato
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002908:Chronic Disease; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D018721:Muscarinic Agonists / Q000633:toxicity; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018721:Muscarinic Agonists; D010862:Pilocarpine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D012601:Scopolamine
keywords: aspartate; glutamate; microdialysis; pilocarpine; temporal lobe epilepsy