Fentanyl-Induced Transformations in Composition of Lipid Droplets in Central Nervous System Cells revealed by Ramanomics.

Abstract

Quantitative characterization of the transformations of subcellular molecular environment in response to fentanyl exposure in human microglia and astrocytes is warranted to provide insight into the regulation of neuroinflammatory responses and neural survival in the scenario of opiate drug addiction. Cytoplasmic lipid droplets (LD) act as depot for exogeneous hydrophobic molecules, such as fentanyl, which can lead to increased drug accumulation and alteration of their metabolism. In the present work, we have used an emerging Ramanomics technique that combines quantitative micro-Raman spectrometry with biomolecular component analysis to unravel fentanyl induced changes in concentrations of phospholipids, sterols, glycogen, sphingomyelin, phosphocholine as well as RNA and proteins, in the LDs of microglia and astrocytes. To our knowledge, this study represents, the first report on the effect of fentanyl overdose in the biomolecular composition of distinct organelles in single live cells, towards therapeutics advances to treat fentanyl addiction and development of diagnostic assays of illicit opiate abuse.