Neural Stem Cells in the Adult Subventricular Zone Oxidize Fatty Acids to Produce Energy and Support Neurogenic Activity.
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.
Centre for Brain Ageing and Vitality, Newcastle University, Newcastle upon Tyne, United Kingdom.|Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.|Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.|Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
Elizabeth A
EA
Stoll
Undergraduate Programme in Biomedical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
Rebecca
R
Makin
Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, USA.
Ian R
IR
Sweet
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
Andrew J
AJ
Trevelyan
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.
Satomi
S
Miwa
Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, USA.
Philip J
PJ
Horner
Centre for Brain Ageing and Vitality, Newcastle University, Newcastle upon Tyne, United Kingdom.|Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.|Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.|Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
Douglass M
DM
Turnbull
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D020547:Lateral Ventricles; D051379:Mice; D058953:Neural Stem Cells / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*
D005227:Fatty Acids
Differentiation; Fatty acid oxidation; Neural stem cell; Neurogenesis; Progenitor; Proliferation