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

Lookup NU author(s): Dr Elizabeth Stoll, Professor Andrew Trevelyan, Dr Satomi Miwa, Emeritus Professor Doug Turnbull

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Neural activity is tightly coupled to energy consumption, particularly sugars such as glucose. Yet 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 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 subventricular zone NSPCs without affecting cellular survival. Finally, higher levels of neurogenesis can be achieved in aged mice by ectopically expressing PGC1a, 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.


Publication metadata

Author(s): Stoll EA, Makin R, Sweet IR, Trevelyan AJ, Miwa S, Horner PJ, Turnbull DM

Publication type: Article

Publication status: Published

Journal: Stem Cells

Year: 2015

Volume: 33

Issue: 7

Pages: 2306-2319

Print publication date: 01/07/2015

Online publication date: 27/04/2015

Acceptance date: 24/03/2015

Date deposited: 07/09/2015

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: Wiley

URL: http://dx.doi.org/10.1002/stem.2042

DOI: 10.1002/stem.2042

PubMed id: PMC4478223


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Funding

Funder referenceFunder name
Newcastle University Centre for Brain Ageing and Vitality - (Economic and Social Research Council)
Newcastle University Centre for Brain Ageing and Vitality - (Engineering and Physical Sciences Research Council)
UK NIHR Biomedical Research Centre in Age and Age Related Diseases award
Newcastle University Centre for Brain Ageing and Vitality - (Biotechnology and Biological Sciences Research Council)
096919/Z/11/ZWellcome Trust Centre for Mitochondrial Research Grant
AG038305NIH
DK17047DRC Cell Functional Analysis Core NIH Grant
G000608-1MRC Centre for Neuromuscular Disease Grant
G0700718Newcastle University Centre for Brain Ageing and Vitality - (Medical Research Council)
G0700718Medical Research Council (MRC)

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