Age and meloxicam attenuate the ischemia/reperfusion-induced down-regulation in the NMDA receptor genes.
This study describes the effect of global brain ischemia followed by 48 h reperfusion, when delayed neuronal death can be already observed. We quantified the mRNA levels of the N-methyl-D-aspartate receptor (NMDAR) subunits and those of the astroglia (glial fibrilar acidic protein, GFAP) and microglia (CD11b) markers using real time PCR on the cerebral cortex and hippocampus of 3- and 18-month-old Sprague-Dawley rats. Data show an ischemia/reperfusion-induced decrease in the mRNA levels of the NMDAR NR1, NR2A and NR2B subunits genes, which contrasts with the increase in the CD11b and GFAP mRNA levels. These effects are attenuated in all the genes studied in 18-month-old animals, suggesting that this mechanism of response is less efficient in aged animals. Western blot assays of NR1, NR2A and NR2B show parallels with the real time PCR data, indicating that the down-regulation of these genes is controlled at the transcriptional level. We suggest that a decrease in the efficiency in the control of the NMDAR transcription could account for the higher vulnerability in aged animals, but it cannot explain by itself differences in the vulnerability to ischemia in different areas of the brain. In the assays of ischemia/reperfusion followed by a treatment with the anti-inflammatory agent meloxicam, we observed that ischemic insult was unable to elicit changes in the NMDAR transcription, thus suggesting that inflammation plays a crucial role in the transcriptional control of these genes.
Montori
Sheyla
S
Area de Biología Celular, Instituto de Biomedicina, Universidad de León, 24071 León, Spain.
Dos-Anjos
Severiano
S
Martínez-Villayandre
Beatriz
B
Regueiro-Purriños
Marta M
MM
Gonzalo-Orden
José M
JM
Ruano
Diego
D
Fernández-López
Arsenio
A
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D008297:Male; D000077239:Meloxicam; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D013843:Thiazines / Q000494:pharmacology* / Q000627:therapeutic use; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam