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The Journal of Neuroscience, September 10, 2003, 23(23):8212-8220

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Brain-Derived Neurotrophic Factor Stimulates Energy Metabolism in Developing Cortical Neurons

Julia Burkhalter, Hubert Fiumelli, Igor Allaman, Jean-Yves Chatton, and Jean-Luc Martin

Institute of Physiology, Faculty of Medicine, University of Lausanne, CH-1005 Lausanne, Switzerland

Brain-derived neurotrophic factor (BDNF) promotes the biochemical and morphological differentiation of selective populations of neurons during development. In this study we examined the energy requirements associated with the effects of BDNF on neuronal differentiation. Because glucose is the preferred energy substrate in the brain, the effect of BDNF on glucose utilization was investigated in developing cortical neurons via biochemical and imaging studies. Results revealed that BDNF increases glucose utilization and the expression of the neuronal glucose transporter GLUT3. Stimulation of glucose utilization by BDNF was shown to result from the activation of Na⁺/K⁺-ATPase via an increase in Na⁺ influx that is mediated, at least in part, by the stimulation of Na⁺-dependent amino acid transport. The increased Na⁺-dependent amino acid uptake by BDNF is followed by an enhancement of overall protein synthesis associated with the differentiation of cortical neurons. Together, these data demonstrate the ability of BDNF to stimulate glucose utilization in response to an enhanced energy demand resulting from increases in amino acid uptake and protein synthesis associated with the promotion of neuronal differentiation by BDNF.

Key words: BDNF; glucose utilization; 2-deoxyglucose; Na⁺ influx; amino acid uptake; protein synthesis; GLUT3

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Received Feb 4, 2003; revised May 21, 2003; accepted May 21, 2003.

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