Genetic inactivation of proglycolytic enzyme Pfkfb3 in astrocytes to investigate neuronal function

Abstract

Neurons use very little glucose through the glycolytic pathway for energy generation, despite their high energy expenditure during neurotransmission (1). The energy requirements of neurons are mostly supplied by oxidative phosphorylation (2). According to the astrocyte-neuron lactate shuttle (3), astrocytic-derived lactate is a major oxidizable substrate for neurons. We have demonstrated that astrocytes, in contrast to neurons, are highly glycolytic cells (4) thus explaining the continuous release of lactate for neuronal use. A key factor responsible for these metabolic shapes is the pro-glycolytic enzyme 6-phosphofructokinase/fructose-2,6-bisphosphatase, isoform 3 (PFKFB3