Neuronal differentiation involves a shift from glucose oxidation to fermentation

  • Maynara Fornazari
  • Isis C. Nascimento
  • Arthur A. Nery
  • Camille C. Caldeira da Silva
  • Alicia J. Kowaltowski
  • Henning Ulrich


Energy metabolism in the adult brain consumes large quantities of glucose, but little is known to date regarding how glucose metabolism changes during neuronal differentiation, a process that is highly demanding energetically. We studied changes in glucose metabolism during neuronal differentiation of P19 mouse embryonal carcinoma cells, E14Tg2A embryonic stem cells as well as during brain development of BLC57 mice. In all these models, we find that neurogenesis is accompanied by a shift from oxidative to fermentative glucose metabolism. This shift is accompanied by both a decrease in mitochondrial enzymatic activities and mitochondrial uncoupling. In keeping with this finding, we also observe that differentiation does not require oxidative metabolism, as indicated by experiments demonstrating that the process is preserved in cells treated with the ATP synthase inhibitor oligomycin. Overall, we provide evidence that neuronal differentiation involves a shift from oxidative to fermentative metabolism, and that oxidative phosphorylation is not essential for this process.


Neuronal differentiation Fermentative glucose metabolism Mitochondrial uncoupling P19 embryonal carcinoma cells E14Tg2A embryonic stem cells 

Supplementary material

10863_2011_9374_MOESM1_ESM.jpg (962 kb)
Supplementary Figure 1 Viability of undifferentiated (UND) P19 cells and cells following completion of neuronal differentiation (DIF). Cell viability was detected by staining for 1 min with 0.004% Trypan Blue as stated in Experimental Procedures. (JPEG 961 kb)
10863_2011_9374_MOESM2_ESM.jpg (973 kb)
Supplementary Figure 2 O2 consumption of P19 cells differentiated in the absence of cytosine-arabinoside. Cells were incubated with Krebs buffer and O2 consumption was estimated as described in Experimental Procedures. Cells were differentiated in the absence of 5 μg/ml cytosine arabinoside which was used to eliminate proliferating glial cells. (JPEG 972 kb)


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Maynara Fornazari
    • 1
  • Isis C. Nascimento
    • 2
  • Arthur A. Nery
    • 1
  • Camille C. Caldeira da Silva
    • 1
  • Alicia J. Kowaltowski
    • 1
  • Henning Ulrich
    • 1
  1. 1.Departamento de Bioquímica, Instituto de QuímicaUniversidade de São PauloSão PauloBrazil
  2. 2.Departmento de Neurologia/NeurocirurgiaUniversidade Federal de São PauloSão PauloBrazil

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