Calcium dependence of damage to mouse motor nerve terminals following oxygen/glucose deprivation.
Calcium dependence of damage to mouse motor nerve terminals following oxygen/glucose deprivation.
复制标题
DOI：
10.1016/j.expneurol.2011.12.020
复制
发表时间：
2012-03
影响因子：
5.3
通讯作者：
Barrett, John N.
中科院分区：
文献类型：
--
作者：
Talbot, Janet D.;David, Gavriel;Barrett, Ellen F.;Barrett, John N.
关键词：
运动神经末梢对缺血/再灌注应激特别敏感。我们将这种应激的体外模型，氧/葡萄糖剥夺（OGD）应用于小鼠神经肌肉制剂，以研究Ca2+如何促进应激诱导的运动末端损伤。使用离子电泳注射荧光[Ca2+]指示剂的测量显示，OGD发病后，终端内[Ca2+]增加。当OGD在静息[Ca2+]增加后20-30分钟内终止时，这些变化有时是可逆的；在其他情况下[Ca2+]保持高，终末变性。在OGD 22分钟和再氧120分钟（32.5°C）后，对终板神经支配进行形态计量学评估。应力诱导的运动终末变性是Ca2+依赖性的。当溶液中含有正常的1.8 mM Ca2+时，应力后终板的中位占用率仅为26%，而当Ca2+不存在时，中位占用率增加到81%。仅在OGD期间去除Ca2+比仅在再氧化期间去除Ca2+更具保护性。通过药物抑制Ca2+进入运动终端的各种途径，包括电压依赖性Ca2+通道（ω-agatoxin-IVA，尼莫地平）和质膜Na+/Ca2+交换器（KB-R7943），部分保留了应激后终板的占用。钙蛋白酶抑制剂VI对Ca2+依赖性蛋白酶的抑制也具有保护作用。这些结果表明，大多数ogd诱导的运动末端损伤是Ca2+依赖性的，抑制Ca2+进入或Ca2+依赖性蛋白水解可以减轻这种损伤。野生型和症状前超氧化物歧化酶1 G93A突变末端对OGD的反应以及对所试药物保护作用的反应无显著差异。
Motor nerve terminals are especially sensitive to an ischemia/reperfusion stress. We applied an in vitro model of this stress, oxygen/glucose deprivation (OGD), to mouse neuromuscular preparations to investigate how Ca2+ contributes to stress-induced motor terminal damage. Measurements using an ionophoretically-injected fluorescent [Ca2+] indicator demonstrated an increase in intra-terminal [Ca2+] following OGD onset. When OGD was terminated within 20–30 min of the increase in resting [Ca2+], these changes were sometimes reversible; in other cases [Ca2+] remained high and the terminal degenerated. Endplate innervation was assessed morphometrically following 22 min OGD and 120 min reoxygenation (32.5 °C). Stress-induced motor terminal degeneration was Ca2+-dependent. Median post-stress endplate occupancy was only 26% when the bath contained the normal 1.8 mM Ca2+, but increased to 81% when Ca2+ was absent. Removal of Ca2+ only during OGD was more protective than removal of Ca2+ only during reoxygenation. Post-stress endplate occupancy was partially preserved by pharmacological inhibition of various routes of Ca2+ entry into motor terminals, including voltage-dependent Ca2+ channels (ω-agatoxin-IVA, nimodipine) and the plasma membrane Na+/Ca2+ exchanger (KB-R7943). Inhibition of a Ca2+-dependent protease with calpain inhibitor VI was also protective. These results suggest that most of the OGD-induced motor terminal damage is Ca2+-dependent, and that inhibition of Ca2+ entry or Ca2+-dependent proteolysis can reduce this damage. There was no significant difference between the response of wild-type and presymptomatic superoxide dismutase 1 G93A mutant terminals to OGD, or in their response to the protective effect of the tested drugs.
登录
查看更多内容
影响因子：
7.3
作者：
Brustovetsky, Tatiana;Brittain, Matthew K.;Brustovetsky, Nickolay
通讯作者：
Brustovetsky, Nickolay
影响因子：
2.5
作者：
ANGAUTPETIT, D;MOLGO, J;FAILLE, L
通讯作者：
FAILLE, L
影响因子：
3.5
作者：
CHIU, AY;ZHAI, P;GURNEY, ME
通讯作者：
GURNEY, ME
影响因子：
2.8
作者：
Eastlack, RK;Groppo, ER;Pedowitz, RA
通讯作者：
Pedowitz, RA
影响因子：
4.8
作者：
Chabwine, J. N.;Talavera, K.;Callewaert, G.
通讯作者：
Callewaert, G.