The cytosolic redox state of astrocytes: Maintenance, regulation and functional implications for metabolite trafficking

Abstract

Astrocytes have important functions in the metabolism of the brain. These cells provide neurons with metabolic substrates for energy production as well as with precursors for neurotransmitter and glutathione synthesis. Both the metabolism of astrocytes and the subsequent supply of metabolites from astrocytes to neurons are strongly affected by alterations in the cellular redox state. The cytosolic redox state of astrocytes depends predominantly on the ratios of the oxidised and reduced partners of the redox pairs NADH/NAD⁺, NADPH/NADP⁺ and GSH/GSSG. The NADH/NAD⁺ pair is predominately in the oxidised state to accept electrons that are produced during glycolysis. In contrast, the redox pairs NADPH/NADP⁺ and GSH/GSSG are biased towards the reduced state under unstressed conditions to provide electrons for reductive biosyntheses and antioxidative processes, respectively. In this review article we describe the metabolic processes that maintain the redox pairs in their desired redox states in the cytosol of astrocytes and discuss the consequences of alterations of the normal redox state for the regulation of cellular processes and for metabolite trafficking from astrocytes to neurons.