Regulation of the Synaptic Vesicle Cycle and Generation of Reactive Oxygen Species in Synaptosomes after Lactate Treatment

Various metabolites can modulate functioning of neuronal presynaptic terminals. We studied the effects of lactate and an agonist of its HCAR1 receptor, 3,5-dihydroxybenzoic acid, on the synaptic vesicle cycle and generation of reactive oxygen species in synaptosomes from the rat brain. In contrast to pyruvate, lactate did not affect the synaptic vesicle cycle at a 4 mM concentration. Using the acridine orange fluorescent probe, we revealed that 3,5-dihydroxybenzoic acid activated endocytosis at a 500 μM concentration. Lactate, but not 3,5-dihydroxybenzoic acid, increased fluorescence of 2',7'-dichlorofluorescein diacetate indicating the generation of reactive oxygen species. Using the MitoSOX fluorescent probe we also showed the formation of superoxide anion in mitochondria after the lactate treatment. Thus, lactate may affect the functioning of neuronal presynaptic terminals due to the formation of reactive oxygen species and activation of endocytosis, which is mediated by HCAR1 lactate receptor.