Aïd Saba, Bosetti Francesca
Brain Physiology and Metabolism Section, National Institute on Aging, National Institute of Health, Bethesda, MD 20892-0947, USA.
Brain Res Bull. 2007 Jun 15;73(1-3):108-13. doi: 10.1016/j.brainresbull.2007.02.015. Epub 2007 Mar 20.
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.
脑老化与炎症变化相关。然而，关于脑花生四烯酸（AA）代谢如何随年龄变化的数据有限且存在差异。AA通过磷脂酶A2（PLA2）从膜磷脂中释放出来，然后由环氧化酶（COX）-1和-2进一步代谢为生物活性前列腺素和血栓烷。我们检测了4、12、24和30月龄大鼠海马和大脑皮质中磷脂酶A2（PLA2）/COX介导的AA代谢途径。24和30月龄时脑内血栓烷B2水平增加两倍，同时12、24和30月龄时海马COX-1 mRNA水平升高。COX-2 mRNA表达仅在30月龄时显著降低。24和30月龄时海马中不依赖钙的iPLA2 mRNA水平降低，而依赖钙的PLA2表达无变化。在大脑皮质中，COX和PLA2的mRNA水平无显著变化。在海马中观察到的AA级联反应的特定变化可能会改变磷脂稳态，并可能增加老化脑对神经炎症的易感性。
