nature-medicine201212-5

来自美国爱荷华大学的研究人员通过小鼠研究发现了小儿脑积水的新病因,研究显示是一个细胞信号传导发生故障从而影响了正常大脑发育相关的未分化脑细胞。他们采用相应药物进行治疗,修复了受到影响的神经前体细胞,缓解了脑积水的病情。

-2012年12月《自然-医学》


中文翻译


【题目】纤毛病变小鼠模型中NG2+PDGFR-α+神经祖细胞的异常发育会导致新生小鼠出现脑积水

【译文】脑积水是一种常见神经障碍,会引起脑室的扩张,伴随较高的死亡率和发病率。大多数新生儿病例病因学还不清楚,可能是涉及多种基因和环境因素的复杂遗传。为新生儿脑积水鉴定分子机制并开发非侵入性治疗模式是需要优先考虑的。本研究利用人纤毛病变巴比二氏综合症(BBS)的脑积水小鼠模型并鉴定了神经祖细胞在新生儿脑积水发病中的作用。我们发现在这种小鼠模型中脑积水是由异常血小板衍生生长因子受体α (PDGFR-α)信号通路造成的,这导致凋亡增加并损害硫酸软骨素粘蛋白4(又名神经元-神经胶质抗原2或NG2)+PDGFR-α+神经祖细胞的增殖。锂盐治疗靶向该通路恢复了BBS突变小鼠中NG2+PDGFR-α+祖细胞增殖,减少了它们的脑室容积。我们的发现证实了神经祖细胞在新生儿脑积水发病中至关重要,并为这种常见神经障碍鉴定了新的治疗靶点。

英文原稿


[Title]: Abnormal development of NG2+PDGFR-α+ neural progenitor cells leads to neonatal hydrocephalus in a ciliopathy mouse model

[Authors]:Calvin S Carter,1, 10 Timothy W Vogel,2, 10 Qihong Zhang,3, 4 Seongjin Seo,4, 5 Ruth E Swiderski,3, 4 Thomas O Moninger,6 Martin D Cassell,7 Daniel R Thedens,8 Kim M Keppler-Noreuil,3 Peggy Nopoulos,9 Darryl Y Nishimura,3 Charles C Searby,3, 4 Kevin Bugge3, 4 & Val C Sheffield3, 4

[Abstract]Hydrocephalus is a common neurological disorder that leads to expansion of the cerebral ventricles and is associated with a high rate of morbidity and mortality. Most neonatal cases are of unknown etiology and are likely to have complex inheritance involving multiple genes and environmental factors. Identifying molecular mechanisms for neonatal hydrocephalus and developing noninvasive treatment modalities are high priorities. Here we use a hydrocephalic mouse model of the human ciliopathy Bardet-Biedl Syndrome (BBS) and identify a role for neural progenitors in the pathogenesis of neonatal hydrocephalus. We found that hydrocephalus in this mouse model is caused by aberrant platelet-derived growth factor receptor α (PDGFR-α) signaling, resulting in increased apoptosis and impaired proliferation of chondroitin sulfate proteoglycan 4 (also known as neuron-glial antigen 2 or NG2)+PDGFR-α+ neural progenitors. Targeting this pathway with lithium treatment rescued NG2+PDGFR-α+ progenitor cell proliferation in BBS mutant mice, reducing their ventricular volume. Our findings demonstrate that neural progenitors are crucial in the pathogenesis of neonatal hydrocephalus, and we identify new therapeutic targets for this common neurological disorder.

原文地址

http://www.nature.com/nm/journal/v18/n12/abs/nm.2996.html

 

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