Chronic mild stress eliminates the neuroprotective effect of Copaxone after CNS injury.
Chronic mild stress eliminates the neuroprotective effect of Copaxone after CNS injury.
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DOI：
10.1016/j.bbi.2012.12.015
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发表时间：
2013-07
影响因子：
15.1
通讯作者：
Kipnis, Jonathan
中科院分区：
文献类型：
--
作者：
Smirnov, Igor;Walsh, James T.;Kipnis, Jonathan
关键词：
Copolymer（Cop）-1，也称为醋酸格拉替雷，是Copaxone的活性化合物，Copaxone是多发性硬化症（MS）患者广泛使用的药物。克帕松通过两种作用机制在MS中起作用，即免疫调节和神经保护。由于免疫系统在抑郁个体中受到抑制或改变，并且由于抑郁症通常与神经系统疾病相关，因此我们有兴趣研究Copaxone的神经保护作用是否在应激诱导的抑郁行为条件下持续存在。我们将小鼠暴露于不可预测的慢性轻度应激4周，然后每隔3天用三次剂量的Copaxone治疗它们，最后一次剂量是在小鼠遭受视神经挤压损伤之前立即给予的。而非应激小鼠表现出强烈的神经保护反应后，Copaxone治疗，这种效果是完全没有小鼠经历慢性轻度应激。有趣的是，当Copaxone与百忧解组合时，Copaxone的神经保护作用重新获得，这表明慢性轻度应激干扰了Copaxone的神经保护作用。这些结果可能揭示了Copaxone的作用机制，并导致新的神经退行性和神经炎症性疾病的联合治疗。
Copolymer (Cop)-1, also known as glatiramer acetate, is an active compound of Copaxone, a drug widely used by patients with multiple sclerosis (MS). Copaxone functions in MS through two mechanisms of action, namely immunomodulation and neuroprotection. Because the immune system is suppressed or altered in depressed individuals, and since depression is often associated with neurological conditions, we were interested in examining whether the neuroprotective effect of Copaxone persists under conditions of stress-induced depressive behavior. We exposed mice to unpredictable chronic mild stress for 4 weeks and then treated them with three doses of Copaxone at 3-day intervals, with the last dose given immediately before the mice underwent a crush injury to the optic nerve. Whereas nonstressed mice exhibited a strong neuroprotective response after Copaxone treatment, this effect was completely absent in mice that underwent chronic mild stress. Interestingly, when Copaxone was combined with Prozac, the neuroprotective effect of Copaxone was regained, suggesting that chronic mild stress interferes with the neuroprotective effect of Copaxone. These results may shed a light on mechanism of action of Copaxone and lead to new combined therapies for neurodegenerative and neuroinflammatory disorders.
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影响因子：
10.6
作者：
Miller, Andrew H.;Maletic, Vladimir;Raison, Charles L.
通讯作者：
Raison, Charles L.
影响因子：
6.6
作者：
Frank, MG;Frank, JLW;Johnson, DR
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影响因子：
3.4
作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.94.20.10821
发表时间：
1997-09-30
影响因子：
11.1
作者：
Aharoni, R;Teitelbaum, D;Arnon, R
通讯作者：
Arnon, R