Glutamate receptor and transporter modifications in rat organotypic hippocampal slice cultures exposed to oxygen-glucose deprivation: the contribution of cyclooxygenase-2.
Meloxicam is a non-steroidal anti-inflammatory drug which has been reported to lessen the ischemic transcriptional effects in some of the glutamatergic system genes as well as to decrease the infarct volume in in vivo assays. In this study, we show how the presence of meloxicam decreases cell mortality in assays of oxygen-glucose deprivation (OGD) in rat organotypic hippocampal slices culture. Mortality was measured using propidium iodide. Transcript levels of some glutamatergic system genes, including vesicular and membrane glutamate transporters (VGLUT1, VGLUT2, GLAST-1A, GLT-1, and EAAC-1) and some glutamatergic receptor subunits (NMDA receptor, GluN1, GluN2A and GluN2B subunits and AMPA receptor, GluA1 and GluA2 subunits) were measured by real-time PCR (qPCR). The transcription of vesicular glutamate transporters and glutamatergic receptor subunits, but not membrane glutamate transporters, was modified by the presence of meloxicam. The study demonstrates the neuroprotective role of meloxicam in organotypic hippocampal slice cultures and shows how meloxicam is able to selectively increase or decrease the OGD-induced changes in the expression of the different glutamatergic system genes studied here. We suggest that the neuroprotective role of meloxicam could be due to a modification in the balance of the expression of some glutamatergic receptor subunits, leading to a different stoichiometry of receptors such as NMDA or AMPA. Thus, meloxicam would decrease the excitotoxicity induced by OGD.
Área de Biología Celular, Instituto de Biomedicina, Universidad de León, 24071 León, Spain.
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Llorente
Sezione di Farmacologia Clinica e Oncologia, Dipartimento di Scienze della Salute, Università di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy.
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Landucci
Sezione di Farmacologia Clinica e Oncologia, Dipartimento di Scienze della Salute, Università di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy.
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Pellegrini-Giampietro
Área de Biología Celular, Instituto de Biomedicina, Universidad de León, 24071 León, Spain. Electronic address: arsenio.fernandez@unileon.es.
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Fernández-López
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005947:Glucose / Q000172:deficiency*; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000378:metabolism*; D000077239:Meloxicam; D018696:Neuroprotective Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism*; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D046509:Tissue Culture Techniques; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D027342:Excitatory Amino Acid Transporter 2; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D017470:Receptors, Glutamate; C493475:Slc17a6 protein, rat; C493466:Slc17a7 protein, rat; C493395:Slc1a2 protein, rat; D013843:Thiazines; D013844:Thiazoles; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D050496:Vesicular Glutamate Transport Proteins; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D005947:Glucose; D000077239:Meloxicam
AMPA; COX-2; EAATs; NMDA; OGD; VGLUTs