Cocaine Mediated Neuroinflammation: Role of Dysregulated Autophagy in Pericytes
Abstract
Cocaine, a known psychostimulant, results in oxidative stress and inflammation. Recent studies from our group have shown that cocaine induces inflammation in glial cells. Our current study was aimed at investigating whether cocaine exposure could also induce inflammation in non-glial cells such as the pericytes with a focus on the endoplasmic reticulum (ER) stress/autophagy axis. Our in vitro findings demonstrated that exposure of pericytes to cocaine resulted in upregulation of the pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in both the intracellular as well as extracellular compartments, thus underpinning pericytes as yet another source of neuroinflammation. Cocaine exposure of pericytes resulted in increased formation of autophagosomes as demonstrated by a time-dependent increase of autophagy markers, with a concomitant defect in the fusion of the autophagosome with the lysosomes. Pharmacological blocking of the sigma 1 receptor underscored its role in cocaine-mediated activation of pericytes. Furthermore, it was also demonstrated that cocaine-mediated dysregulation of autophagy involved upstream activation of the ER stress pathways, with a subsequent downstream production of pro-inflammatory cytokines in pericytes. ...Continue Reading
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Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome
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