Boosting Mitochondrial Biogenesis Diminishes Foam Cell Formation in the Post-Stroke Brain

Sanna H. Loppi, Marco A. Tavera-Garcia, Natalie E. Scholpa, Boaz K. Maiyo, Danielle A. Becktel, Helena W. Morrison, Rick G. Schnellmann, Kristian P. Doyle

Research output: Contribution to journalArticlepeer-review

Abstract

Following ischemic stroke, the degradation of myelin and other cellular membranes surpasses the lipid-processing capabilities of resident microglia and infiltrating macrophages. This imbalance leads to foam cell formation in the infarct and areas of secondary neurodegeneration, instigating sustained inflammation and furthering neurological damage. Given that mitochondria are the primary sites of fatty acid metabolism, augmenting mitochondrial biogenesis (MB) may enhance lipid processing, curtailing foam cell formation and post-stroke chronic inflammation. Previous studies have shown that the pharmacological activation of the β2-adrenergic receptor (β2-AR) stimulates MB. Consequently, our study sought to discern the effects of intensified β2-AR signaling on MB, the processing of brain lipid debris, and neurological outcome using a mouse stroke model. To achieve this goal, aged mice were treated with formoterol, a long-acting β2-AR agonist, daily for two and eight weeks following stroke. Formoterol increased MB in the infarct region, modified fatty acid metabolism, and reduced foam cell formation. However, it did not reduce markers of post-stroke neurodegeneration or improve recovery. Although our findings indicate that enhancing MB in myeloid cells can aid in the processing of brain lipid debris after stroke, it is important to note that boosting MB alone may not be sufficient to significantly impact stroke recovery.

Original languageEnglish (US)
Article number16632
JournalInternational journal of molecular sciences
Volume24
Issue number23
DOIs
StatePublished - Dec 2023

Keywords

  • aging
  • beta-2-adrenergic activation
  • mitochondrial biogenesis
  • stroke

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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