Probing changes in brain esterified oxylipin concentrations during the early stages of pathogenesis in Alzheimer's Disease transgenic rats. (20th November 2022) - Shen, Qing
Highlights: Brain esterified oxylipins were measured in transgenic Alzheimer's Disease (AD) rats. Measurements were performed at 10 months of age when pathology is not established. 8 esterified oxylipins involved in inflammation and resolution were altered in AD rats. The study provides evidence of early brain changes in esterified oxylipins in AD. Abstract: Despite known pathological hallmarks of Alzheimer's Disease (AD) including neuronal loss, gliosis (inflammation), beta-amyloid plaque deposition and neurofibrillary tangle accumulation in the brain, little is known about inflammation resolution in early AD pathogenesis. In the brain, inflammation and resolution pathways are mediated by free oxylipins which are mostly bound (i.e. esterified), and therefore must be released (i.e. become free) to exert bioactivity. Recently, we showed reductions in brain esterified pro-resolving oxylipins in a transgenic rat model of AD (TgF344-AD rat) at 15 months of age, suggesting deficits in the source and availability of free pro-resolving oxylipins. In the present study, we tested whether these changes are discernable earlier in the disease process, i.e., at age of 10 months. We observed significant reductions in esterified pro-resolving 8(9)-epoxyeicosatrienoic acid (8(9)-EpETrE), 13-hydroxyoctadecatrienoic acid (13-HOTrE) and 15-hydroxyeicosapentaenoic acid (15-HEPE) oxylipins, and in pro-inflammatory 13-hydroxy-octadecadienoic acid (13-HODE), 20-hydroxy-eicosatetraenoic acid (20-HETE), 15-deoxy-prostaglandin J2 (15-deoxy-PGJ2) and prostaglandin E2 (PGE2) oxylipins in male and/or female transgenic AD rats compared to wildtype controls. These findings point to a deficit in esterified pro-resolving lipid mediators in the early stages of AD, concident with. changes in esterified lipid mediators involved in promoting inflammation.