Figure 1.

Diverse metabolic phenotypes of brain cells. Neurons produce ATP primarily via mitochondrial oxidative phosphorylation (OXPHOS), but their glycolytic rate is less active than that of astrocytes due to suppressed PFK activity. Both lactate and ketone bodies can enter neurons via monocarboxylate transporter 2 (MCT2). Astrocytes are highly active in glycolysis to produce lactate but less dependent on OXPHOS due to low pyruvate dehydrogenase (PDH) activity. Lactate is generated by lactate dehydrogenase 5 (LDH5) in astrocytes and exported by MCT1 and MCT4. Astrocytes are capable to metabolize fatty acids through β-oxidation. Fatty acids transport into mitochondria is facilitated by carnitine and carnitine palmitoyltransferases (CPTs). Ketone bodies can be generated in astrocytic mitochondria via ketogenesis. Excessive astrocytic glucose can be stored as glycogen, which can be converted back to glucose. Resting microglia have high rate of OXPHOS and low production of reactive oxygen species (ROS), whereas activated microglia produce large amount of ROS and undergo a metabolic reprogramming from OXPHOS toward glycolysis and lactate production.