Phospholipids containing arachidonic acid are decreased in the choroid plexus during aging which can contribute to inflammation

Abstract: The choroid plexus (CP) is a secretory tissue found in each brain ventricle and it produces the cerebrospinal fluid (CSF). As we age, lipid composition of the brain and CP change where the brain generally has lower docosahexaenoic acid (DHA) levels, an omega-3 fatty acid that is a precursor of anti-inflammatory mediators. Our hypothesis was that, like in the brain, phospholipids containing DHA in the CP would be decreased during aging with a concomitant increase in the transcription of genes involved in inflammation and their respective oxylipins/eicosanoids levels. The CP of C57/BL6 male and female mice aged 6-, 12-, 18-, and 24-months (n = 5/sex/age) were dissected. Lipids were extracted and analyzed by a targeted semi-quantitative lipidomic approach. Whole transcriptome of the CP was analyzed by RNA-seq. Oxylipins were analysed by LS-MS/MS. The relative abundance of polar lipids in the CP during aging was unchanged. However, in the phosphatidylcholine (PC) and phosphatidylethanolamine (PE), some species containing arachidonic acid (ARA) abruptly decreased between 18- and 24-months old. In the transcriptomics of CP of mice between 18- and 24-months of age, there was an abrupt upregulation in the expression of genes involved in inflammation and an abrupt downregulation of genes involved in chromatin and neurotransmitter receptor complex. A pilot test confirmed that 63 oxylipids/eicosanoids mediators were detected with less than 30% variation in the mouse CP and these analyses are currently underway. This study potentially provides another mechanistic explanation of brain inflammation by showing that ARA in the membranes of aging CP is consumed at a higher rate than its renewal to generate pro-oxidative mediators in response to upregulation of the transcription of genes involved in inflammation.