Is glutamate dehydrogenase one of the keys to control brain glutamate Homeostasis?

• Autorzy: Waagepetersen H.S.
• Języki publikacji: EN

Abstrakty

EN

Brain glutamate concentration needs to be balanced to avoid excitoxicity. Following glutamatergic neurotransmission astrocytes are responsible for clearance of the synaptic cleft via glutamate transporters. In the astrocyte the conversion of glutamate to glutamine is an essential part of the glutamate-glutamine cycle. But, a substantial amount of glutamate is oxidatively metabolized in the mitochondria, which to a large extent may be dependent on glutamate dehydrogenase (GDH). Thus, astrocytes are likely the main regulator of the brain glutamate concentration, but how do they do it? We have investigated the role of GDH in astrocytes with focus on energy and glutamate neurotransmitter homeostasis. We have used cultured astrocytes originating from CNS‑specific GDH1 knock‑out mice and cultures of astrocytes treated with siRNA against GDH. We find that an impaired GDH activity force glutamate to be only partially oxidized via the truncated TCA cycle and formation of another excitatory amino acid, aspartate. Astrocytes totally lacking GDH exhibit an increased glycolysis and impaired glucose oxidation, supporting that astrocytes are in a need for glutamate oxidation to sustain energy metabolism. FINANCIAL SUPPORT: Lundbeck Foundation

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.22

Twórcy

autor

Waagepetersen H.S.

• Faculty of Health and Medical Sciences, University of Copenhagen, Denmark