Smaller quantal size and faster kinetics of single exocytotic events in chromaffin cells from the APP/PS1 mouse model of Alzheimer's disease
Smaller quantal size and faster kinetics of single exocytotic events in chromaffin cells from the APP/PS1 mouse model of Alzheimer's disease
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DOI：
10.1016/j.bbrc.2012.10.082
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发表时间：
2012-11-30
影响因子：
3.1
通讯作者：
Garcia, Antonio G.
中科院分区：
文献类型：
--
作者：
de Diego, Antonio M. G.;Lorrio, Silvia;Garcia, Antonio G.
在C57小鼠的染色质细胞和阿尔茨海默病（AD）的APP/PS1小鼠模型中测量了单安计胞外事件的动力学。K+去极化引起尖峰的爆发，这表明儿茶酚胺单囊含量的量子释放。对来自10个对照细胞的278个尖峰和来自18个APP/PS1细胞的520个尖峰的动力学分析表明，与前者相比，后者具有以下特征：(i) t（1/2）降低45%；（ii）量子尺寸减小60%；（iii）衰减时间降低50%。钉脚的量子尺寸也缩小了60%。免疫荧光和硫黄素染色显示APP/PSI小鼠肾上腺髓质切片中没有β淀粉样蛋白（A β）负荷，但在皮质和海马中表现出致密的A β斑块。此外，肾上腺髓质乙酰胆碱酯酶染色显示，对照组和APP/PS1小鼠嗜铬细胞内脏胆碱能神经末梢的神经支配无明显差异。这是第一个发现胞吐最后阶段细微差异的报告，这可能是阿尔茨海默病中与A β负荷无关的分泌机制突触功能障碍的指示。(C) 2012爱思唯尔公司版权所有。
The kinetics of single-amperometric exocytotic events has been measured in chromaffin cells of C57 mice and in an APP/PS1 mouse model of Alzheimer's disease (AD). K+ depolarisation causes a burst of spikes that indicate the quantal release of the single-vesicle content of catecholamine. The kinetic analysis of 278 spikes from 10 control cells and 520 spikes from 18 APP/PS1 cells shows the following features of the latter compared with the former: (i) 45% lower t(1/2); (ii) 60% smaller quantal size; (iii) 50% lower decay time. Spike feet also showed 60% smaller quantal size. Immunofluorescence and thioflavin staining showed no amyloid beta (A beta) burden in adrenal medulla slices of APP/PSI mice that however exhibited dense A beta plaques in the cortex and hippocampus. Furthermore, acetylcholinesterase staining of adrenal medulla indicated no apparent differences in the innervation by splanchnic cholinergic nerve terminals of chromaffin cells from control and APP/PS1 mice. This is the first report identifying subtle differences in the last steps of exocytosis that could be an indication of synaptic dysfunction of the secretory machinery not linked to A beta burden in AD. (C) 2012 Elsevier Inc. All rights reserved.