title: Temporal and spatial increase of reactive nitrogen species in the kainate model of temporal lobe epilepsy.
abstract: Steady-state levels of reactive oxygen species (ROS) and oxidative damage to cellular macromolecules are increased in the rodent hippocampus during epileptogenesis. However, the role of reactive nitrogen species (RNS) in epileptogenesis remains to be explored. The goal of this study was to determine the spatial and temporal occurrence of RNS i.e. nitric oxide levels in a rat model of temporal lobe epilepsy (TLE). Rats were injected with a single high dose of kainate and monitored by video for behavioral seizures for 6weeks to determine the onset and severity of chronic seizures. RNS and tissue/mitochondrial redox status (glutathione redox couple and coenzyme A:glutathione redox couple) were measured in the hippocampus at 8h, 24h, 48h, 1wk, 3wk and 6wk following kainate to assess the level of reactive species in subcellular compartments. We observed a biphasic increase in RNS levels with a return to control values at the 48h time point. However, both tissue and mitochondrial redox status showed permanent and significant decreases during the entire time course of epilepsy development. 3 nitrotyrosine (3NT) protein adducts were found to gradually increase throughout epileptogenesis, conceivably as a result of the local environment under oxidative and nitrosative stress. Colocalization of 3NT immunostaining with neuron- or astrocyte-specific markers revealed neuron-specific localization of 3NT in hippocampal principal neurons. Persistent and concurrent glutathione oxidation and nitrosative stress occur during epileptogenesis suggesting a favorable environment for posttranslational modifications.
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Ryan
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Liang
authors.affiliation: Division of Renal Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Rivard
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA. Electronic address: manisha.patel@ucdenver.edu.
authors.forename: Manisha
authors.initials: M
authors.lastname: Patel
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D003065:Coenzyme A / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000150:complications / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007608:Kainic Acid; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D012640:Seizures / Q000209:etiology / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D026361:Reactive Nitrogen Species; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C019305:coenzyme A-glutathione mixed disulfide; D005978:Glutathione; D003065:Coenzyme A; D007608:Kainic Acid; D019803:Glutathione Disulfide
keywords: Mitochondria; Nitrogen species; Oxidative stress; Posttranslational modification; Reactive oxygen species; Temporal lobe epilepsy