PMID- 19631248 OWN - NLM STAT- MEDLINE DCOM- 20100125 LR - 20131121 IS - 1872-9754 (Electronic) IS - 0197-0186 (Linking) VI - 55 IP - 8 DP - 2009 Dec TI - Synaptopathy under conditions of altered gravity: changes in synaptic vesicle fusion and glutamate release. PG - 724-31 LID - 10.1016/j.neuint.2009.07.003 [doi] AB - Glutamate release and synaptic vesicle heterotypic/homotypic fusion were characterized in brain synaptosomes of rats exposed to hypergravity (10 G, 1h). Stimulated vesicular exocytosis determined as KCl-evoked fluorescence spike of pH-sensitive dye acridine orange (AO) was decreased twice in synaptosomes under hypergravity conditions as compared to control. Sets of measurements demonstrated reduced ability of synaptic vesicles to accumulate AO ( approximately 10% higher steady-state baseline level of AO fluorescence). Experiments with preloaded l-[(14)C]glutamate exhibited similar amount of total glutamate accumulated by synaptosomes, equal concentration of ambient glutamate, but the enlarged level of cytoplasmic glutamate measuring as leakage from digitonin-permeabilized synaptosomes in hypergravity. Thus, it may be suggested that +G-induced changes in stimulated vesicular exocytosis were a result of the redistribution of intracellular pool of glutamate, i.e. a decrease in glutamate content of synaptic vesicles and an enrichment of the cytoplasmic glutamate level. To investigate the effect of hypergravity on the last step of exocytosis, i.e. membrane fusion, a cell-free system consisted of synaptic vesicles, plasma membrane vesicles, cytosolic proteins isolated from rat brain synaptosomes was used. It was found that hypergravity reduced the fusion competence of synaptic vesicles and plasma membrane vesicles, whereas synaptosomal cytosolic proteins became more active to promote membrane fusion. The total rate of homo- and heterotypic fusion reaction initiated by Ca(2+) or Mg(2+)/ATP remained unchanged under hypergravity conditions. Thus, hypergravity could induce synaptopathy that was associated with incomplete filling of synaptic vesicles with the neuromediator and changes in exocytotic release. FAU - Krisanova, N V AU - Krisanova NV AD - The Dep. of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha St., Kiev 01601, Ukraine. FAU - Trikash, I O AU - Trikash IO FAU - Borisova, T A AU - Borisova TA LA - eng PT - Journal Article DEP - 20090722 PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Fluorescent Dyes) RN - 3KX376GY7L (Glutamic Acid) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - F30N4O6XVV (Acridine Orange) RN - I38ZP9992A (Magnesium) SB - IM MH - Acridine Orange/pharmacokinetics MH - Adenosine Triphosphate/metabolism MH - Animals MH - Brain/*metabolism/pathology/physiopathology MH - Calcium Signaling/physiology MH - Cell Compartmentation/physiology MH - Cognition Disorders/etiology/metabolism/physiopathology MH - Cytoplasm/metabolism MH - Disease Models, Animal MH - Exocytosis/physiology MH - Fluorescent Dyes/pharmacokinetics MH - Glutamic Acid/*metabolism MH - Hypergravity/*adverse effects MH - Magnesium/metabolism MH - Male MH - Membrane Fusion/physiology MH - Presynaptic Terminals/*metabolism/pathology MH - Rats MH - Rats, Wistar MH - Synaptic Transmission/*physiology MH - Synaptic Vesicles/*metabolism/pathology MH - Synaptosomes EDAT- 2009/07/28 09:00 MHDA- 2010/01/26 06:00 CRDT- 2009/07/28 09:00 PHST- 2009/07/10 00:00 [received] PHST- 2009/07/14 00:00 [accepted] PHST- 2009/07/28 09:00 [entrez] PHST- 2009/07/28 09:00 [pubmed] PHST- 2010/01/26 06:00 [medline] AID - S0197-0186(09)00227-7 [pii] AID - 10.1016/j.neuint.2009.07.003 [doi] PST - ppublish SO - Neurochem Int. 2009 Dec;55(8):724-31. doi: 10.1016/j.neuint.2009.07.003. Epub 2009 Jul 22.