title: Recurrent glutamate stimulations potentiate the hydroxyl radicals response to glutamate.
abstract: Neurotoxicity induced by hydroxyl radicals (OH) release is thought to be involved in a number of acute and chronical neuropathologies of the central nervous system. As far as neurodegenerative processes are concerned, the possible mechanisms giving rise to such OH releases remain poorly understood. In the present study, unanesthetized rats were perfused with a low salicylate solution through a chronic microdialysis cannula implanted into the striatum, and the OH responses to glutamate were analyzed. A single bolus of 3 mM glutamate elicited only minute releases of OH in naive rats. By contrast, recurrent infusions at 1-week intervals of the same glutamate concentration induced a robust OH response. Similar potentiation of the initial response also occurred for a larger glutamate concentration (30 mM). Oppositely, multiple injections of a high (300 mM) glutamate concentration resulted in a slow down of the initial OH response recorded in naive animals. The mechanisms giving rise to such effects are presently unknown. It is, however, clear that repetitive dysfunctions of the glutamate neurotransmission may be sufficient to promote the release of significant amounts of hydroxyl radicals, resulting in a progressive impairment of the astrocytic glutamate transporter, leading to neurodegenerative processes.
authors.affiliation: CRBM, CNRS UPR 1086, Medicinal Chemistry Laboratory, ENSCM, Montpellier, France.
authors.forename: I
authors.initials: I
authors.lastname: Cauquil-Caubère
authors.forename: C
authors.initials: C
authors.lastname: Oxhamre
authors.forename: J M
authors.initials: JM
authors.lastname: Kamenka
authors.forename: G
authors.initials: G
authors.lastname: Barbanel
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000008:administration & dosage*; D062385:Hydroxybenzoates / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D051381:Rats
chemical_list: D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; D018698:Glutamic Acid; C009135:2,3-dihydroxybenzoic acid