Differentiation-Dependent Energy Production and Metabolite Utilization: A Comparative Study on Neural Stem Cells, Neurons, and Astrocytes.
While it is evident that the metabolic machinery of stem cells should be fairly different from that of differentiated neurons, the basic energy production pathways in neural stem cells (NSCs) or in neurons are far from clear. Using the model of in vitro neuron production by NE-4C NSCs, this study focused on the metabolic changes taking place during the in vitro neuronal differentiation. O2 consumption, H(+) production, and metabolic responses to single metabolites were measured in cultures of NSCs and in their neuronal derivatives, as well as in primary neuronal and astroglial cultures. In metabolite-free solutions, NSCs consumed little O2 and displayed a higher level of mitochondrial proton leak than neurons. In stem cells, glycolysis was the main source of energy for the survival of a 2.5-h period of metabolite deprivation. In contrast, stem cell-derived or primary neurons sustained a high-level oxidative phosphorylation during metabolite deprivation, indicating the consumption of own cellular material for energy production. The stem cells increased O2 consumption and mitochondrial ATP production in response to single metabolites (with the exception of glucose), showing rapid adaptation of the metabolic machinery to the available resources. In contrast, single metabolites did not increase the O2 consumption of neurons or astrocytes. In "starving" neurons, neither lactate nor pyruvate was utilized for mitochondrial ATP production. Gene expression studies also suggested that aerobic glycolysis and rapid metabolic adaptation characterize the NE-4C NSCs, while autophagy and alternative glucose utilization play important roles in the metabolism of stem cell-derived neurons.
1 Laboratory of Cellular and Developmental Neurobiology, Institute of Experimental Medicine of Hungarian Academy of Sciences , Budapest, Hungary .|2 Roska Tamás Doctoral School of Sciences and Technology, Faculty of Information Technology and Bionics, Pázmány Péter Catholic University , Budapest, Hungary .
Attila Gy
AG
Jády
3 Department of Medical Biochemistry, Semmelweis University , Budapest, Hungary .
Ádám M
ÁM
Nagy
1 Laboratory of Cellular and Developmental Neurobiology, Institute of Experimental Medicine of Hungarian Academy of Sciences , Budapest, Hungary .
Tímea
T
Kőhidi
4 Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine of Hungarian Academy of Sciences , Budapest, Hungary .
Szilamér
S
Ferenczi
3 Department of Medical Biochemistry, Semmelweis University , Budapest, Hungary .
László
L
Tretter
1 Laboratory of Cellular and Developmental Neurobiology, Institute of Experimental Medicine of Hungarian Academy of Sciences , Budapest, Hungary .
Emília
E
Madarász
D020155:3-Hydroxybutyric Acid / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019069:Cell Respiration / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D005973:Glutamine / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D055442:Metabolome; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D019289:Pyruvic Acid / Q000378:metabolism
D007773:Lactates; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D005973:Glutamine; D019289:Pyruvic Acid; D017346:Protein Serine-Threonine Kinases; D005947:Glucose; D020155:3-Hydroxybutyric Acid