Sivko R. Glutamate transport in rat brain nerve terminals under conditions of changes in the level of cholesterol in the membrane structures

Object: exocytosis and active glutamate transport in rat brain nerve terminals. Methods: preparative biochemistry, spectrofluorimetry, flow cytometry, confocal microscopy, photon correlation spectroscopy, spectrophotometry, statistical analysis. It was shown for the first time that the addition of methyl-beta-cyclodextrin (MCD) to isolated brain nerve terminals (synaptosomes) leads to a dose-dependent dissipation of the proton gradient of synaptic vesicles. It was shown a reduction of transporter-dependent glutamate release in cholesterol-deficient synaptosomes. The treatment of nerve terminals by complex MCD-cholesterol that enriches membrane with cholesterol causes an increase in the initial velocity of glutamate uptake and synaptic vesicle acidification. So, a decrease in the level of membrane cholesterol may be used for neuroprotection under pathological conditions including stroke, cerebral hypoxia/ischemia, traumatic brain injury that were associated with an increase in glutamate uptake reversal. Viсe versa in norm, a decrease in the concentration of membrane cholesterol may cause neurotoxic consequences resulted from the enhancement of the extracellular glutamate level because of a decrease in glutamate uptake.