Morphological and functional changes in innervation of a fast forelimb muscle in SOD1-G85R mice.
Morphological and functional changes in innervation of a fast forelimb muscle in SOD1-G85R mice.
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DOI：
10.1016/j.nbd.2012.07.011
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发表时间：
2012-12
影响因子：
6.1
通讯作者：
David G
中科院分区：
文献类型：
--
作者：
Nguyen KT;Zhang Z;Barrett EF;David G
表达人超氧化物歧化酶1（hSOD 1）突变的小鼠（家族性肌萎缩侧索硬化症模型）的肌肉终板变得失去神经支配。这种去神经支配在快肢肌中尤其明显，并且先于运动神经元胞体的死亡。本研究使用在神经元中表达黄色荧光蛋白（YFP）的小鼠来研究与表达野生型（wt）hSOD 1的小鼠相比，在症状前和有症状的hSOD 1-G85 R小鼠中支配快速前肢肌肉（肘上肌，ETA）的轴突和运动末梢的形态和功能的变化。在症状前SOD 1-G85 R小鼠中，运动终板（使用荧光标记的α-银环蛇毒素鉴定）受运动终末支配的百分比仍然很高，但在有症状的小鼠中降至约50%。当小鼠出现症状时，ETA神经中大直径（≥ 4 µm）轴突的数量也减少，终板神经支配与大直径轴突的数量相关性最好。运动神经末梢功能进行了评估，使用终端YFP荧光诱发的动作电位列车的变化;不同成分的pH依赖性YFP信号反映刺激诱导的Ca 2+进入和囊泡外/内吞。大多数可见的运动终末（>90%）在前和症状性hSOD 1-G85 R小鼠中仍然能够对神经刺激作出反应，但具有功能改变。症状前终端的反应表明减少酸化和增加囊泡释放，而症状终端表现出增加酸化和减少囊泡释放。大多数剩余的终端能够对神经刺激作出反应的事实表明，运动终端保护疗法可能有助于保护fALS小鼠的神经肌肉功能。
Muscle endplates become denervated in mice that express mutations of human superoxide dismutase 1 (hSOD1), models of familial amyotrophic lateral sclerosis. This denervation is especially marked in fast limb muscles, and precedes death of motor neuron somata. This study used mice that expressed yellow fluorescent protein (YFP) in neurons to investigate changes in the morphology and function of axons and motor terminals inervating a fast forelimb muscle (epitrochleoanconeus, ETA) in presymptomatic and symptomatic hSOD1-G85R mice, compared to those in mice that express wild-type (wt) hSOD1. The percentage of endplates (identified using fluorescently-labeled α-bungarotoxin) innervated by motor terminals remained high in presymptomatic SOD1-G85R mice, but fell to ~50% in symptomatic mice. The number of large diameter (≥ 4 µm) axons in the ETA nerve also decreased as mice became symptomatic, and endplate innervation correlated best with the number of large diameter axons. Motor terminal function was assessed using changes in terminal YFP fluorescence evoked by trains of action potentials; different components of the pH-dependent YFP signals reflect stimulation-induced Ca2+ entry and vesicular exo/endocytosis. Most visible motor terminals (>90%) remained capable of responding to nerve stimulation in both pre- and symptomatic hSOD1-G85R mice, but with functional alterations. Responses in presymptomatic terminals suggested reduced acidification and increased vesicular release, whereas symptomatic terminals exhibited increased acidification and reduced vesicular release. The fact that most remaining terminals were able to respond to nerve stimulation suggests that motor terminal-protective therapies might contribute to preserving neuromuscular function in fALS mice.
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影响因子：
5.3
作者：
Fischer, LR;Culver, DG;Glass, JD
通讯作者：
Glass, JD
影响因子：
25
作者：
Pun, S;Santos, AF;Caroni, P
通讯作者：
Caroni, P
影响因子：
6.1
作者：
Lladó, J;Haenggeli, C;Maragakis, NJ
通讯作者：
Maragakis, NJ
影响因子：
11.2
作者：
BRADLEY, WG;GOOD, P;ADELMAN, LS
通讯作者：
ADELMAN, LS
DOI：
10.1113/jphysiol.2008.153569
发表时间：
2008-07-01
期刊：
The Journal of physiology
影响因子：
--
作者：
Rogozhin AA;Pang KK;Bukharaeva E;Young C;Slater CR
通讯作者：
Slater CR