RNA-Seq analysis of E4FAD mouse brain cortex to evaluate the impact of omega-6 fatty acid docosapentaenoic acid on neuroinflammation

Purpose: In this study, we report on an effective anti-inflammatory lipid, linoleic acid (LA) metabolite docosapentaenoic acid (DPAn-6) treatment of aged humanized EFAD mice with advanced AD pathology. We also report the associations of neuroinflammatory and/or activated microglial markers with neurodegeneration in vivo. Methods: DPAn-6 was administered to the E4FAD mice by oral gavage for three weeks, then brain tissue was collected for the study. Total RNA was qualified using an Agilent BioAnalyzer of High Sensitivity RNA ScreenTapeÒ for Eukaryotic RNA Analysis and 1 µg was used for poly(A) mRNA selection and library construction with IlluminaÒ Platforms KAPA mRNA HyperPrep kit (KK8580 08098115702) according to the manufacturer's instructions (KR1352 – v4.17). Results: We found that DPAn-6 reduced mRNA expressions of inflammatory markers of Il1rl2, Il6ra, Il6st, Tnfrsf1b, Tnfsf10, Il10rb; microglial markers of Tmem119, CD68 and TREM2; and caspase markers of Casp2, Casp6 and Casp8. Further, DPAn-6 increased mRNA expressions of ADCYAP1, VGF, and neuronal pentraxin 2 in parallel, all of which were inversely correlated with inflammatory and microglial markers. Conclusions: We first reportd that DPAn-6 modulated neuroinflammatory responses towards resolution and improvement of neurodegeneration in the late stages of AD models. Overall design: Brain cortex mRNA profiles of DPAn-6-treated E4FAD mice.