Neuroprotective effect of erythropoietin on anesthesia-induced neurotoxicity through the modulation of autophagy in Caenorhabditis elegans

Bon Wook Koo, Hyun Jung Shin, Sooyoung Jeon, Jung Hyun Bang, Sang Hwan Do, Hyo Seok Na

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: The anti-oxidative, anti-inflammatory, and anti-apoptotic effects of erythro-poietin may provide neuroprotective effects. Erythropoietin also modulates autophagy signaling that may play a role in anesthesia-induced neurotoxicity (AIN). Herein, we investigated whether AIN can be attenuated by the neuroprotective effect of erythropoietin in the Caenorhabditis elegans (C. elegans). Methods: Synchronized worms were divided into the control, Iso, EPO, and EPO-Iso groups. The chemotaxis index (CI) was evaluated when they reached the young adult stage. The lgg-1::GFP-positive puncta per seam cell were used to determine the autophagic events. The erythropoietin-mediated pathway of autophagy was determined by measuring the genetic expression level of let-363, bec-1, atg-7, atg-5, and lgg-3. Results: Increased lgg-1::GFP puncta were observed in the Iso, EPO, and EPO-Iso groups. In the Iso group, only the let-363 level decreased significantly as compared to that in the control group (P = 0.009). bec-1 (P < 0.001), atg-5 (P = 0.012), and lgg-3 (P < 0.001) were expressed significantly more in the EPO-Iso group than in the Iso groups. Repeated isoflurane exposure during development decreased the CI. Erythropoietin could restore the decreased CI by isoflurane significantly in the EPO-Iso group. Conclusions: Erythropoietin showed neuroprotective effects against AIN and modulated the autophagic pathway in C. elegans. This experimental evidence of erythropoietin-related neuroprotection against AIN may be correlated with the induced autophagic degradation process that was sufficient for handling enhanced autophagy induction in erythropoietin-treated worms.

Original languageEnglish
Pages (from-to)384-391
Number of pages8
JournalKorean journal of anesthesiology
Volume77
Issue number3
DOIs
StatePublished - Jun 2024

Bibliographical note

Publisher Copyright:
© The Korean Society of Anesthesiologists, 2024.

Keywords

  • Anesthesia-induced neurotoxicity
  • Autophagy
  • Caenorhabditis elegans
  • Erythropoietin
  • Isoflurane
  • Neuroprotection
  • Toxicity

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