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
Highlights
Neural stem/progenitor cells (NSPCs), which retain the capacity to produce new neurons and glia in the adult mammalian brain, reside in the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone of hippocampal dentate gyrus (DG) [1, 2]
We demonstrate that neural stem cells derived from the mouse SVZ do not require glucose to sustain oxygen consumption, unlike other cell types that have been characterized in the adult brain
We assessed whether enzymes required for fatty acid oxidation were present in neural stem/progenitor cells (NSPCs) located within neurogenic areas of the adult brain
Summary
Neural stem/progenitor cells (NSPCs), which retain the capacity to produce new neurons and glia in the adult mammalian brain, reside in the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone of hippocampal dentate gyrus (DG) [1, 2]. As NSPCs reside in a “neurogenic niche” fortified by blood vessels and astrocytes [5], these cells have direct access to contents in the bloodstream, including substrates to fuel energy metabolism. We investigated the substrates required by adult mammalian neural stem cells to maintain their metabolic and neurogenic activity. Catabolism, the production of energy in the form of ATP, is necessary to sustain cellular activity. The adult brain primarily depends upon the oxidation of carbohydrates such as glucose to fuel energy production.
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