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The neuro-protective role of telomerase via TERT/TERF-2 in the acute phase of spinal cord injury

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Abstract

Purpose

To investigate the interaction of telomerase activity and telomere length on neuro-protection or neuro-degeneration effects after spinal cord injury (SCI).

Methods

A contusive SCI model was developed using 56 Sprague–Dawley rats. Seven rats were allocated into acute injury phase groups (1, 3, 8, 24, and 48 h), and sub-acute and chronic injury phase groups (1, 2, and 4 weeks). Telomerase activity was assessed by telomerase reverse transcriptase (TERT) and telomeric repeat binding factor-2 (TERF-2). Differentiation of activated neural stem cells was investigated by co-expression of neuronal/glial cell markers. Apoptosis expression was also investigated by caspase-3, 8, and 9 using terminal deoxynucleotidyl transferase dUTP nick end labelling staining. Immunofluorescence staining and western blotting were performed for quantitative analyses.

Results

Expression of TERT increased gradually until 24 h post-injury, and was decreased following SCI (P < 0.05). TERF-2 also was increased following SCI until 24 h post-injury and then decreased with time (P < 0.05). Co-localization of TERT and TERF-2 was higher at 24 h post-injury. High expression of TERT was seen in neurons (Neu N Ab), however, expression of TERT was relatively lower in astrocytes and oligodendrocytes. Apoptosis analysis showed persistent high expression of caspases-3, -9, and -8 during the observation period.

Conclusions

Increased TERT and TERF-2 activity were noted 24 h post-injury in the acute phase of SCI with TERF-2 maintaining telomeric-repeat length. Our results suggest that increased activity of telomere maintenance may be related to neuro-protective mechanisms against subsequent apoptosis resulting from DNA damage after acute SCI.

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Funding

This research was supported by the 2017–2018 Korea Medical Institute Research Grant.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Inje University Sanggye Paik Hospital, College of Medicine, Inje University, Seoul, Korea

    Dong-Gune Chang & Hong Jin Kim

  2. Department of Orthopaedic Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Jang-Woon Kim, Young-Hoon Kim & Sang-Il Kim

  3. Department of Orthopaedic Surgery, College of Medicine, Kyung Hee University at Gangdong, Dongnam-ro, Gangdong-Gu, 892, Seoul, Republic of Korea

    Kee-Yong Ha

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Contributions

Conceptualization, D.G.C., J.W.K, and K.Y.H.; Methodology, D.G.C., and J.W.K.; Validation, J.W.K., and H.J.K.; Formal analysis, J.W.K. and H.J.K.; Investigation, D.G.C, J.W.K, H.J.K, and K.Y.H.; Writing—Original Draft, D.G.C, and J.W.K.; Writing—Review & Editing, H.J.K., Y.H.K., S.I.K. and K.Y.H.; Funding Acquisition, H.K.Y.; Resources, D.G.C., J.W.K, and K.Y.H.; Supervision, K.Y.H.

Corresponding author

Correspondence to Kee-Yong Ha.

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The authors declare no competing interests.

Ethical approval

All procedures involving animals were in compliance with the Laboratory Animal Welfare Act and the Guidelines and Policies for Rodent Survival Surgery, as required by the Animal Studies Committee of the Catholic University of Korea (IACUC Approval No. 2014-0192-02).

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Chang, DG., Kim, JW., Kim, H.J. et al. The neuro-protective role of telomerase via TERT/TERF-2 in the acute phase of spinal cord injury. Eur Spine J 32, 2431–2440 (2023). https://doi.org/10.1007/s00586-023-07561-3

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  • DOI: https://doi.org/10.1007/s00586-023-07561-3

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