Cocaine Mediated Neuroinflammation: Role of Dysregulated Autophagy in Pericytes

Molecular Neurobiology
Susmita SilShilpa Buch

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

References

Mar 1, 1981·Journal of Ethnopharmacology·G BarnettR Resnick
Jun 1, 1997·Journal of Neurochemistry·M C NassogneP J Courtoy
Jul 20, 1999·Experimental and Molecular Pathology·F D KolodgieR Virmani
Apr 3, 2002·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Pascal RomieuTangui Maurice
Sep 3, 2002·Neuroscience and Biobehavioral Reviews·Tangui MauriceRae R Matsumoto
May 6, 2003·The Journal of Pharmacology and Experimental Therapeutics·Teruo Hayashi, Tsung-Ping Su
May 26, 2005·Pharmacological Reviews·Brian T Hawkins, Thomas P Davis
Oct 11, 2005·Neuro-oncology·Gabriele Bergers, Steven Song
Sep 8, 2006·Neurochemistry International·H Fai PoonFiona C Crawford
Nov 30, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Navneet K DhillonShilpa J Buch
Nov 10, 2009·International Review of Neurobiology·Hari S SharmaRanjana Patnaik
Oct 15, 2010·Nature·Annika ArmulikChrister Betsholtz
Dec 16, 2010·Autophagy·Ashley R Winslow, David C Rubinsztein
Feb 4, 2011·Current Opinion in Cell Biology·Soledad MatusClaudio Hetz
Apr 22, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Honghong YaoShilpa Buch
Jul 5, 2011·Journal of Cellular and Molecular Medicine·Karen M DoyleAfshin Samali
Jul 19, 2011·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Shilpa BuchJohn Wang
Jul 1, 2009·Expert Review of Clinical Pharmacology·Rae R Matsumoto
Dec 29, 2011·Administration and Policy in Mental Health·Elizabeth B RobertsonEve E Reider
May 18, 2012·Current HIV Research·Shilpa BuchTsung-Ping Su
May 23, 2012·The Journal of Experimental Medicine·Doris ProebstlSussan Nourshargh
Jun 21, 2012·Neurotoxicity Research·Kenneth H ClarkCharles W Bradberry
Jul 4, 2012·Frontiers in Pharmacology·Sharanya M KousikPaul M Carvey
Sep 6, 2012·Journal of Cellular and Molecular Medicine·Shinsuke NakagawaMichal Toborek
Jan 16, 2013·Immunology and Cell Biology·Sarah A JonesJames Harris
May 24, 2014·Journal of Vascular Research·Peter C StaporWalter Lee Murfee
Feb 6, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jerel FieldsEliezer Masliah
Nov 6, 2015·Frontiers in Microbiology·Sabyasachi DashJui Pandhare
Nov 11, 2015·Proceedings of the National Academy of Sciences of the United States of America·Shang-Yi A TsaiTsung-Ping Su
Dec 15, 2015·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yuri PersidskySlava Rom
Dec 29, 2015·Frontiers in Bioscience (Landmark Edition)·Lindolfo da Silva MeirellesNance Beyer Nardi
Jan 21, 2016·Proceedings of the National Academy of Sciences of the United States of America·Prasun GuhaSolomon H Snyder
May 7, 2016·Nature Reviews. Neuroscience·Marina E Wolf
May 27, 2016·Nature Neuroscience·Melanie D SweeneyBerislav V Zlokovic

❮ Previous
Next ❯

Citations

Jan 23, 2019·Brain : a Journal of Neurology·Luc BertrandMichal Toborek
Aug 15, 2019·Journal of Investigative Medicine High Impact Case Reports·Edward C MaderLionel A Branch
Jul 12, 2020·International Journal of Molecular Sciences·Maria LucaAntonina Luca
Jul 17, 2020·Frontiers in Neuroscience·Emely PimentelThangavel Samikkannu
Nov 16, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yinjie LiLibo Zou
Aug 25, 2021·Current HIV/AIDS Reports·Susmita SilShilpa Buch

❮ Previous
Next ❯

Methods Mentioned

BETA
Protein Assay
ELISA
PCR
transfection

Software Mentioned

GraphPad Prism
AxioVs 40
ImageJ

Related Concepts

Related Feeds

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.