Neural stem cells in the adult subventricular zone oxidize fatty acids to produce energy and support neurogenic activity

Elizabeth A. Stoll, Rebecca Makin, Ian R. Sweet, Andrew J. Trevelyan, Satomi Miwa, Philip J. Horner, Douglass M. Turnbull

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Neural activity is tightly coupled to energy consumption, particularly sugars such as glucose. However, we find that, unlike mature neurons and astrocytes, neural stem/progenitor cells (NSPCs) do not require glucose to sustain aerobic respiration. NSPCs within the adult subventricular zone (SVZ) express enzymes required for fatty acid oxidation and show sustained increases in oxygen consumption upon treatment with a polyunsaturated fatty acid. NSPCs also demonstrate sustained decreases in oxygen consumption upon treatment with etomoxir, an inhibitor of fatty acid oxidation. In addition, etomoxir decreases the proliferation of SVZ NSPCs without affecting cellular survival. Finally, higher levels of neurogenesis can be achieved in aged mice by ectopically expressing proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), a factor that increases cellular aerobic capacity by promoting mitochondrial biogenesis and metabolic gene transcription. Regulation of metabolic fuel availability could prove a powerful tool in promoting or limiting cellular proliferation in the central nervous system. Stem Cells 2015;33:2306-2319

Original languageEnglish (US)
Pages (from-to)2306-2319
Number of pages14
JournalSTEM CELLS
Volume33
Issue number7
DOIs
StatePublished - Jul 1 2015

Keywords

  • Differentiation
  • Fatty acid oxidation
  • Neural stem cell
  • Neurogenesis
  • Progenitor
  • Proliferation

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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