| Neuroprotective effect of erythropoietin on anesthesia-induced neurotoxicity through the modulation of autophagy in Caenorhabditis elegans |
Bon-Wook Koo1,2 
, Hyun-Jung Shin1,2
, Sooyoung Jeon3, Jung Hyun Bang1, Sang-Hwan Do1,2
, Hyo-Seok Na1,2
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1Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
2Department of Anesthesiology and Pain Medicine, Seoul National University, Seoul, Korea
3National Dental Care Center for Persons with Special Needs, Seoul National University Dental Hospital, Seoul, Korea |
Corresponding author:
Hyo-Seok Na, Tel: +82-31-787-7507, Fax: +82-31-787-4063,
Email: hsknana@gmail.com
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Received: 30 October 2023 • Revised: 9 January 2024 • Accepted: 15 January 2024 |
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| Abstract |
Background
The anti-oxidative, anti-inflammatory, and anti-apoptotic effects of erythropoietin 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. |
| Key Words:
Anesthesia-induced neurotoxicity; Autophagy; Caenorhabditis elegans; Erythropoietin; Isoflurane; Neuroprotection |
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