Data on the brain arachidonic acid (AA) metabolism during normal aging are limited and discrepant. AA is released from membrane phospholipids by phospholipase A2 (PLA2) and then further metabolized to bioactive prostaglandins and thromboxanes by cyclooxygenases (COX) -1 and -2. We examined the PLA2COX-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 B2 level in 24 and 30 months was accompanied by increased hippocampal COX-1 mRNA levels at 12, 24, and 30 months. The upregulation of COX-1, which is predominantly expressed in glia, may be associated with glial activation reported in aging. COX-2 mRNA expression was significantly decreased only at 30 months. Hippocampal calcium-independent iPLA2 mRNA levels were decreased at 24 and 30 months without any change in calcium-dependent PLA2 expression. Since iPLA2 is thought to selectively release docosahexaenoic acid (DHA) from membrane phospholipids, its downregulation might contribute to alter phospholipid homeostasis. In the cerebral cortex, mRNA levels of COX and PLA2 were not significantly changed. The specific changes in the AA cascade observed in the hippocampus, which is critical for memory, may alter phospholipids homeostasis and possibly increase the susceptibility of the aging brain to neuroinflammation.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Intramural Research (Z01)
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National Institute on Aging
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Aid, Saba; Bosetti, Francesca (2007) Gene expression of cyclooxygenase-1 and Ca(2+)-independent phospholipase A(2) is altered in rat hippocampus during normal aging. Brain Res Bull 73:108-13
Weerasinghe, Gayani R; Coon, Steven L; Bhattacharjee, Abesh Kumar et al. (2006) Regional protein levels of cytosolic phospholipase A2 and cyclooxygenase-2 in Rhesus monkey brain as a function of age. Brain Res Bull 69:614-21