Methamphetamine compromises gap junctional communication in astrocytes and neurons

Paul Castellano, Chisom Nwagbo, Luis R. Martinez, Eliseo A. Eugenin

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Methamphetamine (meth) is a central nervous system (CNS) stimulant that results in psychological and physical dependency. The long-term effects of meth within the CNS include neuronal plasticity changes, blood-brain barrier compromise, inflammation, electrical dysfunction, neuronal/glial toxicity, and an increased risk to infectious diseases including HIV. Most of the reported meth effects in the CNS are related to dysregulation of chemical synapses by altering the release and uptake of neurotransmitters, especially dopamine, norepinephrine, and epinephrine. However, little is known about the effects of meth on connexin (Cx) containing channels, such as gap junctions (GJ) and hemichannels (HC). We examined the effects of meth on Cx expression, function, and its role in NeuroAIDS. We found that meth altered Cx expression and localization, decreased GJ communication between neurons and astrocytes, and induced the opening of Cx43/Cx36 HC. Furthermore, we found that these changes in GJ and HC induced by meth treatment were mediated by activation of dopamine receptors, suggesting that dysregulation of dopamine signaling induced by meth is essential for GJ and HC compromise. Meth-induced changes in GJ and HC contributed to amplified CNS toxicity by dysregulating glutamate metabolism and increasing the susceptibility of neurons and astrocytes to bystander apoptosis induced by HIV. Together, our results indicate that connexin containing channels, GJ and HC, are essential in the pathogenesis of meth and increase the sensitivity of the CNS to HIV CNS disease.

Original languageEnglish (US)
Pages (from-to)561-575
Number of pages15
JournalJournal of neurochemistry
Volume137
Issue number4
DOIs
StatePublished - May 1 2016

Keywords

  • HIV
  • apoptosis
  • cocaine
  • connexin
  • drugs

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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