title: Kainic acid-induced changes in the opioid/nociceptin system and the stress/toxicity pathways in the rat hippocampus.
abstract: Excitotoxicity is a contributing factor to the pathogenesis of acute or chronic neurodegenerative disease states. Kainic acid (KA) is an excitotoxic substance and the administration of it to rodents induces seizure activity (status epilepticus, SE) and leads to neurodegeneration. In this study the effect of KA-induced excitotoxicity on the G-protein activations and the gene expression levels of the opioid/nociceptin system receptors as MOPr, KOPr, DOPr, ORL-1, and PNOC (N/OFQ) were investigated, and the regulator effect of naloxone (Nal) on the gene expressions of the opioid system receptors against KA-induced seizures in the rat hippocampus was tested. In addition, the expression levels of stress-toxicity genes were assessed in the hippocampus following KA-induced excitotoxicity in order to determine the potential genetic targets which can be helpful for neuroprotective interventions. Our results indicate that the KA-induced excitotoxicity increased the mRNA levels of MOPr, DOPr, KOPr, PNOC, and ORL-1. However, G-protein activations of MOPr, DOPr, and KOPr remained relatively unchanged while both the potency and efficacy of N/OFQ were significantly increased. The PCR array data showed that KA-induced excitotoxicity altered the expression levels of genes in the cellular stress or toxicity pathways. Our data suggests that the induction of the opioid/nociceptin system may be involved in the cellular stress response following a neurodegenerative insult and that the genes modulated by the KA-treatment in the stress-toxicity pathways may be evaluated as targets of potential neuroprotective interventions.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ege University, 35100 Bornova, Izmir, Turkey.
authors.forename: Guliz
authors.initials: G
authors.lastname: Armagan
authors.forename: Engin
authors.initials: E
authors.lastname: Bojnik
authors.forename: Ezgi
authors.initials: E
authors.lastname: Turunc
authors.forename: Lutfiye
authors.initials: L
authors.lastname: Kanit
authors.forename: Ozge
authors.initials: O
authors.lastname: Gündüz Çinar
authors.forename: Sandor
authors.initials: S
authors.lastname: Benyhe
authors.forename: Anna
authors.initials: A
authors.lastname: Borsodi
authors.forename: Ayfer
authors.initials: A
authors.lastname: Yalcin
mesh_terms: D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D018847:Opioid Peptides / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000235:genetics / Q000502:physiology*; D013226:Status Epilepticus / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology*; D000097629:Nociceptin
chemical_list: D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin