Glutamate Dehydrogenase (GDH) is essential to sustain energy metabolism in astrocyte cultures

Research output: Contribution to conferencePosterResearch

Glutamate (glu) is the most abundant excitatory neurotransmitter in the central nervous system and astrocytic clearance of glu is essential for avoidance of glu induced excitotoxicity. Continuance of astrocytic glu removal relies upon metabolism of glu within the astrocyte. Glu entering the astrocytes may either be amidated to glutamine as part of the glu-glutamine cycle or metabolized in the mitochondrial matrix to alpha-ketoglutarate (aKG). The conversion to aKG is catalyzed either by glu dehydrogenase (GDH) or a transaminase. The GDH catalyzed deamination of glu is an energy producing reaction and it also provides an increased pool of TCA cycle intermediates. Thus, GDH is positioned at an intriguing and important place on the metabolic chart having potential impact on both brain energy and glu homeostasis. To investigate the role of GDH in the brain, a CNS specific GDH knock-out (KO) mouse has been constructed. Experiments using cultured astrocytes from the GDH brain KO mice and “wild type” littermates have been conducted. Cytosolic ATP production was measured on-line in living astrocyte cultures infected with luciferase. The ATP production was monitored upon glu and glucose (glc) exposure. The GDH brain KO failed to respond to glu but exhibited an increased ATP production after glc addition. In line with this the metabolism of [U-13C]glc was augmented in the GDH brain KO astrocyte cultures. Thus we find that GDH is essential to sustain the energy status in astrocytes.
Original languageEnglish
Publication date2010
Publication statusPublished - 2010
Event9th International Conference on Brain Energy Metabolism - Budapest, Hungary
Duration: 7 Jul 201012 Jul 2010
Conference number: 9

Conference

Conference9th International Conference on Brain Energy Metabolism
Number9
CountryHungary
CityBudapest
Period07/07/201012/07/2010

ID: 241157751