Lipidomic Signatures in Microglial Extracellular Vesicles During Acute Inflammation: A Gateway to Neurological Biomarkers

作者：Nikita Ollen‐Bittle, Wenxuan Wang, Kimberly M. Bean, Shuang Zhao, Adriana Zardini Buzatto, Yifei Dong, Liang Li, Shawn N. Whitehead · 发表于：Journal of Neurochemistry · 年份：2025 · DOI：10.1111/jnc.70309 · 被引用次数：3 · 研究领域：Extracellular vesicles in disease、Neuroinflammation and Neurodegeneration Mechanisms、interferon and immune responses

Extracellular vesicles (EVs) are membrane-bound vesicles released from all cells throughout the body, including the central nervous system, and are known to carry both membrane-bound proteins and cargo reflective of their cell of origin. EVs show promise as neurological disease biomarkers due to their molecular makeup reflecting their parent-cell composition signature and due to their ability to cross the blood-brain barrier. To date, the vast majority of research in this field has explored the protein profiles of EVs; however, lipids play an important role not only in the formation of EVs, but also in mediating cellular function and the pathological progression of many neurodegenerative conditions. Herein, we take a critical first step in determining the potential utility of EV lipids as biomarkers in neurological disease. In vitro we exposed BV-2 microglia to either control media or media containing lipopolysaccharides (LPS), a known pro-inflammatory stimulus, for 24 h then isolated both the cells and their EVs and performed LC-MS/MS. For the first time, we reveal distinct lipidomic changes can differentiate resting versus pro-inflammatory microglia and their EVs, while distinct lipids are preserved between EVs and their parent cell. Moreover, we add to current literature by demonstrating acute pro-inflammatory activation of microglia results in the activation and suppression of distinct lipidomic pathways. Finally, we demonstrate that analysis of lipid-based relationships ...