Pharmacological inhibition of spinal cord injury-stimulated ribosomal biogenesis does not affect locomotor outcome

Ewa Kilanczyk, Kariena R. Andres, Justin Hallgren, Sujata Saraswat Ohri, Marikki Laiho, Scott R. Whittemore, Michal Hetman

Research output: Contribution to journalArticle

Abstract

After unresolved endoplasmic reticulum stress, recovery of protein synthesis including increased expression of ribosomal components and translation factors may induce cell death. Using a mouse model of moderate contusive spinal cord injury (SCI) at the T9 level, upregulation of ribosomal biogenesis was observed in the injury epicenter at 24 h after trauma. Such upregulation coincided with endoplasmic reticulum stress response as previously reported in this model. It was also accompanied by changes in expression of many other genes associated with translational regulation. Systemic treatment with a pharmacological inhibitor of RNA-Polymerase-1, BMH-21 reduced rRNA transcription in the spinal cord. Moreover, in the injury epicenter, treatment with BMH-21 increased expression of oligodendrocyte-specific transcripts including Mbp and Cldn11 at 3 days post injury. Although such findings may suggest at least transient reduction of oligodendrocyte death, locomotor outcome was mostly unaffected except slightly accelerated recovery of hindlimb function at week 2 post-injury. Therefore, at least in mice, RNA-Polymerase-1 does not appear to be a robust target for therapies to protect spinal cord tissue after contusion. However, these findings raise an interesting possibility that altered rate of ribosomal biogenesis contributes to the apparent translational reprogramming after contusive SCI. Such a reprogramming could be a major regulator of SCI-induced gene expression.

Original languageEnglish (US)
Pages (from-to)153-157
Number of pages5
JournalNeuroscience Letters
Volume642
DOIs
StatePublished - Mar 6 2017

Keywords

  • Cell death
  • Neuroprotection
  • Pharmacotherapy
  • Ribosomal biogenesis
  • Spinal cord injury
  • White matter loss

ASJC Scopus subject areas

  • Neuroscience(all)

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