Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

Susmita Sil, Palsamy Periyasamy, Minglei Guo, Shannon Callen, Shilpa J Buch

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

A recent study from our lab has revealed a link between morphine-mediated autophagy and synaptic impairment. The current study was aimed at investigating whether morphine-mediated activation of astrocytes involved the ER stress/autophagy axis. Our in vitro findings demonstrated upregulation of GFAP indicating astrocyte activation with a concomitant increase in the production of proinflammatory cytokines in morphine-exposed human astrocytes. Using both pharmacological and gene-silencing approaches, it was demonstrated that morphine-mediated defective autophagy involved upstream activation of ER stress with subsequent downstream astrocyte activation via the μ-opioid receptor (MOR). In vivo validation demonstrated preferential activation of ER stress/autophagy axis in the areas of the brain not associated with pain such as the basal ganglia, frontal cortex, occipital cortex, and the cerebellum of morphine-dependent rhesus macaques, and this correlated with increased astrocyte activation and neuroinflammation. Interventions aimed at blocking either the MOR or ER stress could thus likely be developed as promising therapeutic targets for abrogating morphine-mediated astrocytosis.

Original languageEnglish (US)
Pages (from-to)6713-6733
Number of pages21
JournalMolecular Neurobiology
Volume55
Issue number8
DOIs
StatePublished - Aug 1 2018

Keywords

  • Astrocytosis
  • Defective autophagy
  • ER stress
  • Morphine
  • Neuroinflammation
  • Rhesus macaques

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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