A single dose of neuron-binding human monoclonal antibody improves spontaneous activity in a murine model of demyelination.
A single dose of neuron-binding human monoclonal antibody improves spontaneous activity in a murine model of demyelination.
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DOI：
10.1371/journal.pone.0026001
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Rodriguez M
中科院分区：
文献类型：
--
作者：
Denic A;Macura SI;Warrington AE;Pirko I;Grossardt BR;Pease LR;Rodriguez M
我们的实验室证明，一种天然的人血清抗体sHIgM12，在体外与神经元结合并促进神经突生长。我们产生了一个重组形式，rHIgM12，具有相同的属性。易感小鼠品系的泰勒氏鼠脑脊髓炎病毒（TMEV）的脑内感染导致慢性脱髓鞘疾病，其具有类似于多发性硬化的进行性形式的进行性轴突损失和神经功能障碍。为了研究rHIgM12对TMEV感染小鼠运动功能的影响，我们监测了数周的自发夜间活动。夜间行为是啮齿类动物神经功能的敏感指标，因为预期最大活动变化发生在正常活动的夜间监测期间。在治疗前8天将小鼠置于活动箱中以收集基线自发活动。治疗后，在8周内连续记录各组的活动。我们选择长的8周监测期有两个原因：（1）我们先前证明IgM诱导的髓鞘再生在治疗后5周存在，和（2）TMEV诱导的脱髓鞘疾病在该菌株中进展非常缓慢。由于观察期较长且数据集较大，研究原始未过滤记录可能难以了解治疗组之间的差异。为了清楚地描绘高度波动的原始数据的变化，我们应用了三种不同的方法：（1）合并，（2）应用高斯低通滤波器（GF）和（3）多项式拟合。使用这三种方法中的每一种，我们表明，与对照IgM和生理盐水相比，rHIgM12的早期治疗诱导水平和垂直运动功能的改善，而后期治疗仅改善水平活动。rHIgM 12不改变正常未感染小鼠的活动。这项研究支持了这样的假设，即用神经元结合IgM治疗不仅在体外保护神经元，而且还影响功能性运动改善。
Our laboratory demonstrated that a natural human serum antibody, sHIgM12, binds to neurons in vitro and promotes neurite outgrowth. We generated a recombinant form, rHIgM12, with identical properties. Intracerebral infection with Theiler's Murine Encephalomyelitis Virus (TMEV) of susceptible mouse strains results in chronic demyelinating disease with progressive axonal loss and neurologic dysfunction similar to progressive forms of multiple sclerosis. To study the effects of rHIgM12 on the motor function of TMEV-infected mice, we monitored spontaneous nocturnal activity over many weeks. Nocturnal behavior is a sensitive measure of rodent neurologic function because maximal activity changes are expected to occur during the normally active night time monitoring period. Mice were placed in activity boxes eight days prior to treatment to collect baseline spontaneous activity. After treatment, activity in each group was continuously recorded over 8 weeks. We chose a long 8-week monitoring period for two reasons: (1) we previously demonstrated that IgM induced remyelination is present by 5 weeks post treatment, and (2) TMEV-induced demyelinating disease in this strain progresses very slowly. Due to the long observation periods and large data sets, differences among treatment groups may be difficult to appreciate studying the original unfiltered recordings. To clearly delineate changes in the highly fluctuating original data we applied three different methods: (1) binning, (2) application of Gaussian low-pass filters (GF) and (3) polynomial fitting. Using each of the three methods we showed that compared to control IgM and saline, early treatment with rHIgM12 induced improvement in both horizontal and vertical motor function, whereas later treatment improved only horizontal activity. rHIgM12 did not alter activity of normal, uninfected mice. This study supports the hypothesis that treatment with a neuron-binding IgM not only protects neurons in vitro, but also influences functional motor improvement.
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影响因子：
14.5
作者：
McGavern, DB;Murray, PD;Rodriguez, M
通讯作者：
Rodriguez, M
影响因子：
3.6
作者：
Melnick, SM;Dow-Edwards, DL
通讯作者：
Dow-Edwards, DL
影响因子：
5.1
作者：
Pohl, Daniela;Rostasy, Kevin;Hanefeld, Folker
通讯作者：
Hanefeld, Folker
DOI：
10.1093/jnen/63.5.461
发表时间：
2004-05-01
影响因子：
3.2
作者：
Warrington, AE;Bieber, AJ;Rodriguez, M
通讯作者：
Rodriguez, M
影响因子：
6.8
作者：
AKAIKE, H
通讯作者：
AKAIKE, H