Proteomic phenotyping of CNS cells exposed to inflammatory stimuli and opioids

Neuroinflammation is a complex mechanism linked to several brain diseases and many undesired side effects associated with opioid treatments, and results from the interactions of cells within the CNS such as astrocytes and brain endothelial cells. Albeit astrocytes are the most abundant cells of the CNS there is currently limited information about their role in neuroinflammatory processes and their involvement in the onset of morphine-induced side effects. In the present thesis we combined in vitro models and mass spectrometry-based proteomics to investigate and characterise the inflammatory phenotype of human astrocytes, brain endothelial cells and their released extracellular vesicles at protein level. Moreover, we extensively studied the effects, at translational and post-translational level, of morphine and its two main metabolites M3G and M6G in human astrocytes, and reported new information which is important to deepen our knowledge about the participation of these cells in the development of opioid-induced side effects.