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Original Research | Open Access

Lithium ameliorates spinal cord injury through endoplasmic reticulum stress-regulated autophagy and alleviated apoptosis through IRE1 and PERK/eIF2α signaling pathways

Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China
Department of Orthopaedics, Xi'an International Medical Center Hospital, Xi'an, China

1 These authors contributed to the work equally and should be regarded as cofirst authors.

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Abstract

Objective

This study aims to investigate the role of apoptosis and autophagy under endoplasmic reticulum (ER) stress in a lithium-treated SCI model.

Methods

We established a rat thoracic 10 (T10) spinal cord contusion model and observed its therapeutic effect by intraperitoneal (IP) injection of lithium. Histological and behavioral recovery with or without lithium injection were evaluated after rat spinal cord injury. In addition, we employed an oxygen-glucose deprivation (OGD)-PC12 cell model to study the effects of lithium on OGD-PC12 cell apoptosis, autophagy and ER stress.

Results

We found that lithium administration to SCI rats reduced neuronal apoptosis and autophagy, restored rat locomotor function by reducing ER stress via IRE1 and PERK/eIF2α pathways. In vitro experiments confirmed that upon lithium treatment, OGD-PC12 cells resisted ER stress caused by thapsigargin (TG) via the IRE1 and PERK/eIF2α signaling pathways.

Conclusion

Lithium attenuated neuronal apoptosis and autophagy, and facilitates the recovery after spinal cord injury through ameliorating ER stress, providing a new therapeutic mechanism for lithium to treat SCI.

Keywords

Spinal cord injuryLithiumAnti-apoptosisAnti-autophagyER stress

References

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Journal of Neurorestoratology
Volume 11 Issue 4,
December 2023
Article number: 100081
DOI: 10.1016/j.jnrt.2023.100081

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Wang F, Zhang C, Zhang Q, et al. Lithium ameliorates spinal cord injury through endoplasmic reticulum stress-regulated autophagy and alleviated apoptosis through IRE1 and PERK/eIF2α signaling pathways. Journal of Neurorestoratology, 2023, 11(4): 100081. https://doi.org/10.1016/j.jnrt.2023.100081

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Received: 23 July 2023
Revised: 07 October 2023
Accepted: 08 October 2023
Published: 12 October 2023
© 2023 The Authors.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).