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

Eur Spine J. 2023 Jul;32(7):2431-2440. doi: 10.1007/s00586-023-07561-3. Epub 2023 May 10.

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.

Keywords: Apoptosis; Neuroprotective mechanism; Spinal cord injury; Telomerase activity; Telomerase reverse transcriptase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Neurons / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / metabolism
  • Spinal Cord Injuries*
  • Telomerase* / genetics
  • Telomerase* / metabolism
  • Telomerase* / pharmacology

Substances

  • Telomerase