Early upregulation of hippocampal 5-lipoxygenase following systemic administration of kainate to rats

5-Lipoxygenase (5-LO; arachidonate:oxygen 5-oxidoreductase, EC 1.13.11.34) is the enzyme responsible for the first step in the formation of inflammato ry leukotrienes from arachidonic acid. 5-LO is expressed in hippocampal neu rons. Increased formation of leukotrienes was found in the hippocampus of r ats in which seizures were induced by a glutamate receptor agonist, kainate . Expression of the 5-LO gene can be stimulated by vitamin D3 and suppresse d by the pineal hormone melatonin. Here we hypothesize that kainate also st imulates 5-LO expression in the hippocampus. Kainate was injected intraperi toneally (10 mg/kg). Rats were sacrificed 3 hr later and their hippocampi w ere dissected and total RNA was extracted and processed for quantitative re verse transcription/polymerase chain reaction (RT-PCR) assay of 5-LO and cy clophilin (cyc) mRNAs. Mutated primers were used as internal standards to a ssay attomol quantities of these two specific mRNAs per microgram of total RNA. Fixed hippocampal slices were processed for 5-LO immunostaining and Ni ssl staining.(assay of cell damage). Kainate induced about a 2.5-fold incre ase in 5-LO mRNA and triggered a redistribution of 5-LO-like immunoreactivi ty from the pyramidal cell bodies into the dendrites of these neurons, part icularly in the CA3 area. The results suggest that glutamate receptor-media ted signaling may modify the expression of neuronal 5-LO and that this enzy me might be involved in glutamate receptor-mediated neuronal plasticity and /or degeneration.