5-Lipoxygenase and cyclooxygenase mRNA expression in rat hippocampus: early response to glutamate receptor activation by kainate

Recent research has identified in central nervous system neurons the expres sion of two enzymes from the inflammatory pathway of the metabolism of arac hidonic acid, the 5-lipoxygenase (5LOX) and the cyclooxygenase-2 (COX2). Ex pression of both enzymes appears to be upregulated during aging; upregulate d 5LOX/COX2 expression in neurons may be responsible for the increased neur onal vulnerability to degeneration. Involvement of the excitatory neurotran smitter glutamate in aging-associated neurodegeneration has also been sugge sted. Stimulation of glutamate receptors by kainic acid (kainate) has been shown independently to affect the brain expression of 5LOX or COX2. Using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) assa y to measure the contents of mRNAs we found 3 h after kainate injection (in traperitoneally; 10 mg/kg) increased mRNA levels of 5LOX and COX2, but not that of COX1 in the hippocampus of rats. Pretreatment with the COX2 inhibit or NS-398 (9 mg/kg, 1 h prior to kainate) inhibited the kainate-stimulated increase of 5LOX and COX2 mRNA levels. Our results indicate that hippocampa l expression of both 5LOX and COX2 increases rather promptly when glutamate receptors are stimulated by kainate. The mechanism of how NS-398 inhibits this action of kainate should be further investigated. (C) 2000 Elsevier Sc ience Inc. All rights reserved.