The biphasic NAD(P)H fluorescence response of astrocytes to dopamine reflects the metabolic actions of oxidative phosphorylation and glycolysis

Abstract

The NAD(+)/NADH redox pair constitutes an important metabolic node connecting catabolic pathways to energy production. We took advantage of the fluorescence of NADH to monitor changes in NADH levels by 2-photon laser scanning microscopy in cultured cortical astrocytes and acutely isolated brain slices in response to dopamine (DA), a major neurotransmitter involved in modulation of attention, motivation, and learning. DA induced a dose-dependent biphasic response of the NAD(P)H fluorescence signal, consisting of an initial decrease followed by a subsequent increase. This response was mediated by D1-receptors, protein kinase A, and 5'-AMP-activated protein kinase signaling. While the initial decrease could be inhibited by blocking mitochondrial respiratory chain, the increase was inhibited by blocking glycolysis. Finally, activation of DA receptors on astrocytes in acutely isolated mouse cortical brain slices also induced an increase in the NAD(P)H fluorescence signal. We conclude that DA activates two opposing components of astrocytic metabolism with different kinetics. This response of the astroglial metabolism might contribute to fine-tuned participation of astrocytes to neuronal activity and functional states of the brain.