Anesthetic agents and neuronal autophagy. What we know and what we don’t

Lili Xu, Jianjun Shen, Patrick M. McQuillan, Zhiyong Hu

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Background: Ethanol is known to have both γ-Aminobutyric acid agonist and N-methyl-D-aspartate antagonist characteristics similar to commonly used volatile anesthetic agents. Recent evidence demonstrates that autophagy can reduce the development of ethanol induced neurotoxicity. Recent studies have found that general anesthesia can cause long-term impairment of both mitochondrial morphogenesis and synaptic transmission in the developing rat brain, both of which are accompanied by enhanced autophagy activity. Autophagy may play an important role in general anesthetic mediated neurotoxicity. Methods: This review outlines the role of autophagy in the development of anesthetic related neurotoxicity and includes an explanation of the role of autophagy in neuronal cell survival and death, the relationship between anesthetic agents and neuronal autophagy, possible molecular and cellular mechanisms underlying general anesthetic agent induced activation of neuronal autophagy in the developing brain, and potential therapeutic approaches aimed at modulating autophagic pathways. Results: In a time-and concentration-dependent pattern, general anesthetic agents can disrupt intracellular calcium homeostasis which enhances both autophagy and apoptosis activation. The degree of neural cell injury may be ultimately determined by the interplay between autophagy and apoptosis. It appears likely that the increase in calcium flux associated with some anesthetic agents disrupts lysosomal function. This results in an over-activation of en-dosomal-lysosomal trafficking causing mitochondrial damage, reactive oxygen species up-regulation, and lipid peroxidation. Conclusion: Autophagy may play a role in the development of anesthetic related neurotoxicity. Understanding this may lead to strategies or therapies aimed at preventing or ameliorating general anesthetic agent mediated neurotoxicity.

Original languageEnglish (US)
Pages (from-to)908-916
Number of pages9
JournalCurrent Medicinal Chemistry
Volume25
Issue number8
DOIs
StatePublished - Mar 1 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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