Gene expression of cyclooxygenase-1 and Ca(2+)-independent phospholipase A(2) is altered in rat hippocampus during normal aging.

Brain aging is associated with inflammatory changes. However, data on how the brain arachidonic acid (AA) metabolism is altered as a function of age are limited and discrepant. AA is released from membrane phospholipids by phospholipase A(2) (PLA(2)) and then further metabolized to bioactive prostaglandins and thromboxanes by cyclooxygenases (COX)-1 and -2. We examined the phospholipase A(2) (PLA(2))/COX-mediated AA metabolic pathway in the hippocampus and cerebral cortex of 4-, 12-, 24- and 30-month-old rats. A two-fold increase in brain thromboxane B(2) level in 24 and 30 months was accompanied by increased hippocampal COX-1 mRNA levels at 12, 24, and 30 months. COX-2 mRNA expression was significantly decreased only at 30 months. Hippocampal Ca(2+)-independent iPLA(2) mRNA levels were decreased at 24 and 30 months without any change in Ca(2+)-dependent PLA(2) expression. In the cerebral cortex, mRNA levels of COX and PLA(2) were not significantly changed. The specific changes in the AA cascade observed in the hippocampus may alter phospholipids homeostasis and possibly increase the susceptibility of the aging brain to neuroinflammation.