Effects of treatments on inflammatory and apoptotic markers in the CNS of mice with globoid cell leukodystrophy.
Effects of treatments on inflammatory and apoptotic markers in the CNS of mice with globoid cell leukodystrophy.
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DOI：
10.1016/j.brainres.2009.09.017
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发表时间：
2009-12-01
期刊：
影响因子：
2.9
通讯作者：
Wenger, David A.
中科院分区：
文献类型：
--
作者：
Luzi, Paola;Abraham, Ronnie M.;Rafi, Mohammad A.;Curtis, Mark;Hooper, D. Craig;Wenger, David A.
关键词：
球样细胞脑白质营养不良（GLD）或克拉伯病是一种神经退行性疾病引起的溶酶体酶半乳糖苷酶（GALC）的缺乏。GALC缺乏导致中枢和外周神经系统的进行性脱髓鞘。炎症细胞和增加的细胞因子和趋化因子水平存在于GLD小鼠的CNS中，并且可能在该疾病的发病机制中起重要作用。在这项研究中，我们评估了非甾体抗炎药，如吲哚美辛和布洛芬，米诺环素，四环素类似物与神经保护和抗凋亡特性，对疾病的进展，使用转基因小鼠模型的GLD。实时定量PCR用于分析免疫/炎症反应的几种标志物的表达。检测不同月龄小鼠皮质、小脑和脊髓中IL-6、TNF-α、MIP-1β、MCP-1、iNOS/NOS 2、CD 11b、CD 68、CD 4和CD 8 mRNA水平。此外，还将药物治疗与骨髓移植（BMT）进行了比较。药物治疗显著延长了治疗小鼠的寿命，并降低了研究的几种免疫相关因子的水平。然而，BMT产生了最戏剧性的改进。在BMT处理的小鼠中，脊髓中的因子比小脑更快地正常化，除了CD 68。接受抗炎药和骨髓移植的小鼠小脑中凋亡细胞的数量减少。这些研究表明联合治疗在GLD治疗中可能发挥作用。
Globoid cell leukodystrophy (GLD) or Krabbe disease is a neurodegenerative disorder caused by the deficiency of the lysosomal enzyme galactocerebrosidase (GALC). GALC deficiency results in a progressive demyelination of the central and peripheral nervous systems. Inflammatory cells and increased levels of cytokines and chemokines are present in the CNS of GLD mice and may play a significant role in the pathogenesis of the disease. In this study we evaluate the effect of non-steroidal anti-inflammatory drugs, such as indomethacin and ibuprofen, and minocycline, a tetracycline analog with neuroprotective and anti-apoptotic properties, on the progression of the disease using a transgenic mouse model of GLD. Real-time quantitative PCR was used to analyze the expression of several markers of the immune/inflammatory response. IL-6, TNF-α, MIP-1β, MCP-1, iNOS/NOS2, CD11b, CD68, CD4 and CD8 mRNA levels were measured in cortex, cerebellum and spinal cord of untreated and treated affected mice at different ages. In addition, the pharmacological treatments were compared to bone marrow transplantation (BMT). The pharmacological treatments significantly extended the life-span of the treated mice and reduced the levels of several of the immuno-related factors studied. However, BMT produced the most dramatic improvements. In BMT-treated mice, factors in the spinal cord were normalized faster than the cerebellum, with the exception of CD68. There was a decrease in the number of apoptotic cells in the cerebellum of mice receiving anti-inflammatory drugs and BMT. These studies indicate a possible role for combined therapy in the treatment of GLD.
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影响因子：
82.9
作者：
Chen, M;Ona, VO;Friedlander, RM
通讯作者：
Friedlander, RM
影响因子：
3.8
作者：
Luzi, P;Rafi, MA;Wenger, DA
通讯作者：
Wenger, DA
影响因子：
5.6
作者：
Kurkowska-Jastrzebska, I;Babiuch, M;Czlonkowska, A
通讯作者：
Czlonkowska, A
影响因子：
11.2
作者：
Jeyakumar, M;Smith, DA;Platt, FM
通讯作者：
Platt, FM
影响因子：
12.4
作者：
Rafi, MA;Rao, HZ;Wenger, DA
通讯作者：
Wenger, DA