Monocarboxylates and glucose utilization as energy substrates in rat brain slices under selective glial poisoning-a³¹P NMR study

Abstract

We have investigated effects of various energy substrates including glucose, lactate and pyruvate on the recovery of the high energy phosphate levels after high-K+ stimulation in rat brain slices by using³¹P NMR. It was found that lactate, pyruvate and glucose almost equally supported the recovery of phosphocreatine (PCr) levels after high-K+ stimulation (60 mM, 8 min) in artificial cerebrospinal fluid (ACSF). In iodoacetic acid (IAA) and fluorocitrate (FC)-pretreated slices, whereasglucosewas unable to be utilized, the recovery of the PCr level after high-K+ stimulation in ACSF containinglactatewas completely abolished, the recovery of the PCr in ACSF containingpyruvatewas unaffected. These results indicate that neurons themselves can utilize pyruvate as an exogenous energy substrate, but not lactate, without glial support. In intact brain, glucose may be metabolized to pyruvate in glial cells and then transported to neurons as an energy substrate. These suggest an astrocyte-neuronpyruvateshuttle mechanism of the brain energy metabolismin vivo.

We also investigated the effect of ischemic-preconditioning in FC-pretreated slices, which showed that the PCr levels recovered substantially in ACSF containing lactate after high-K+ stimulation. This indicates that after the preconditioning, such as ischemia, neurons themselves acquired the ability to utilizelactateas an energy substrate. (Mol Cell Biochem244:77-81, 2003)