Impact of Lactate on Mitochondrial Activity in Endothelial Cells Exposed in vitro to the Acute Toxic Effect of beta-Amyloid

We found that in the in vitro model of Alzheimer’s type neurodegeneration based on the toxic action of beta-amyloid on cultured brain cells, the presence of lactate in the extracellular space in a dose-dependent manner reduces mitochondrial activity in brain microvessel endothelial cells. Lactate monocarboxylate transporter (MCT) blockade has the same effect, but the stimulation of lactate GPR81 receptors on the plasma membrane of these cells increases mitochondrial activity. This suggests that a high extracellular lactate concentration inhibits mitochondrial activity in endothelial cells, but not due to the action on GPR81 receptors. Most likely, the effects of GPR81 are significant in the presence of lower extracellular lactate concentrations. Since the development of Alzheimer’s disease is known to be accompanied by a decreased expression of MCT isoforms that determine lactate transport and metabolism in brain cells, our data indicate that MCT dysregulation in Alzheimer’s disease promotes the development of mitochondrial dysfunction, while the reproduction of the effects of extracellular lactate through activation of GPR81 receptors partially compensates for such alterations.