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Beckervordersandforth, R.* ; Ebert, B. ; Schäffner, I.* ; Moss, J.* ; Fiebig, C.* ; Shin, J.* ; Moore, D.L.* ; Ghosh, L.* ; Trinchero, M.F.* ; Stockburger, C.* ; Friedland, K.* ; Steib, K. ; von Wittgenstein, J.* ; Keiner, S.* ; Redecker, C.* ; Hölter, S.M. ; Xiang, W.* ; Wurst, W. ; Jagasia, R. ; Schinder, A.F.* ; Ming, G.l.* ; Toni, N.* ; Jessberger, S.* ; Song, H.* ; Lie, D.C.C.*

Role of mitochondrial metabolism in the control of early lineage progression and aging phenotypes in adult hippocampal neurogenesis.

Neuron 93, 560-573.e6 (2017)
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Precise regulation of cellular metabolism is hypothesized to constitute a vital component of the developmental sequence underlying the life-long generation of hippocampal neurons from quiescent neural stem cells (NSCs). The identity of stage-specific metabolic programs and their impact on adult neurogenesis are largely unknown. We show that the adult hippocampal neurogenic lineage is critically dependent on the mitochondrial electron transport chain and oxidative phosphorylation machinery at the stage of the fast proliferating intermediate progenitor cell. Perturbation of mitochondrial complex function by ablation of the mitochondrial transcription factor A (Tfam) reproduces multiple hallmarks of aging in hippocampal neurogenesis, whereas pharmacological enhancement of mitochondrial function ameliorates age-associated neurogenesis defects. Together with the finding of age-associated alterations in mitochondrial function and morphology in NSCs, these data link mitochondrial complex function to efficient lineage progression of adult NSCs and identify mitochondrial function as a potential target to ameliorate neurogenesis-defects in the aging hippocampus. Beckervordersandforth, Ebert et al. demonstrate that mitochondrial complex function functionally demarcates an early developmental step in adult hippocampal neurogenesis and identify mitochondrial dysfunction as a candidate target to counter age-associated neurogenesis deficits.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Adult Neurogenesis ; Aging ; Metabolism ; Mitochondria ; Stem Cells; Neural Stem-cells; Oxidative-phosphorylation; Progenitor Proliferation; Enhancer Piracetam; Energy-metabolism; Transgenic Mice; Dentate Gyrus; Brain; Dysfunction; Dynamics
ISSN (print) / ISBN 0896-6273
e-ISSN 1097-4199
Journal Neuron
Quellenangaben Volume: 93, Issue: 3, Pages: 560-573.e6 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed