title: Neuronal-astrocyte metabolic interactions: understanding the transition into abnormal astrocytoma metabolism.
abstract: Brain function depends on complex metabolic interactions among only a few different cell types, with astrocytes providing critical support for neurons. Astrocyte functions include buffering the extracellular space, providing substrates to neurons, interchanging glutamate and glutamine for synaptic transmission with neurons, and facilitating access to blood vessels. Whereas neurons possess highly oxidative metabolism and easily succumb to ischemia, astrocytes rely more on glycolytic metabolism and hence are less susceptible tolack of oxygen. Astrocytoma cells seem to retain basic metabolic mechanisms of astrocytes; for example, they show a high glycolytic rate, lactate extrusion, ability to flourish under hypoxia, and opportunistic use of mechanisms to enhance cell division and maintain growth. Differences in metabolism between neurons and astrocytes may also extend to astrocytoma cells, providing therapeutic opportunities against astrocytomas, including sensitivity to acetate, a high rate of glycolysis and lactate extrusion, glutamate uptake transporters, differential sensitivities of monocarboxylate transporters, presence of glycogen, high interlinking with gap junctions, use of nicotinamide adenine dinucleotide phosphate for lipid synthesis, using different isoforms of synthetic enzymes (e.g. isocitrate dehydrogenase, pyruvate carboxylase, pyruvate kinase, lactate dehydrogenase), and different glucose uptake mechanisms. These unique metabolic susceptibilities may augment conventional therapeutic attacks based on cell division differences and surface receptors alone.
authors.affiliation: Neurosurgery and Neurobiology, Duke University Medical Center, and Research and Surgery Services, Durham VAMC, Durham, NC 27710, USA. dennis.turner@duke.edu
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Turner
authors.forename: David Cory
authors.initials: DC
authors.lastname: Adamson
mesh_terms: D000085:Acetates / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001254:Astrocytoma / Q000378:metabolism* / Q000503:physiopathology*; D001808:Blood Vessels / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000378:metabolism*
chemical_list: D000085:Acetates; D018698:Glutamic Acid