Time-to-treatment window and cross-sex potential of β2-adrenergic receptor-induced mitochondrial biogenesis-mediated recovery after spinal cord injury

Natalie E. Scholpa, Epiphani C. Simmons, Josh D. Crossman, Rick G. Schnellmann

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Mitochondrial dysfunction is a well-characterized consequence of spinal cord injury (SCI). We previously reported that treatment with the FDA-approved β2-adrenergic receptor agonist formoterol beginning 8 h post-SCI induces mitochondrial biogenesis (MB) and improves body composition and locomotor recovery in female mice. To determine the time-to-treatment window of formoterol, female mice were subjected to 80 kdyn contusion SCI and daily administration of vehicle or formoterol (0.3 mg/kg) beginning 24 h after injury. This delayed treatment paradigm improved body composition in female mice by 21 DPI, returning body weight to pre-surgery weight and restoring gastrocnemius mass to sham levels; however, there was no effect on locomotor recovery, as measured by the Basso-Mouse Scale (BMS), or lesion volume. To assess the cross-sex potential of formoterol, injured male mice were treated with vehicle or formoterol (0.3 or 1.0 mg/kg) beginning 8 h after SCI. Formoterol also improved body composition post-SCI in male mice, restoring body weight and muscle mass regardless of dose. Interestingly, however, improved BMS scores and decreased lesion volume was observed only in male mice treated with 0.3 mg/kg. Additionally, 0.3 mg/kg formoterol induced MB in the gastrocnemius and injured spinal cord, as evidenced by increased MB protein expression and mitochondrial number. These data indicate that formoterol treatment improves recovery post-SCI in both male and female mice in a dose- and initiation time-dependent manner. Furthermore, formoterol-induced functional recovery post-SCI is not directly associated with peripheral effects, such as muscle mass and body weight.

Original languageEnglish (US)
Article number115366
JournalToxicology and Applied Pharmacology
Volume411
DOIs
StatePublished - Jan 15 2021

Keywords

  • Formoterol
  • Locomotor recovery
  • Mitochondrial biogenesis
  • Spinal cord injury

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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