Galectin-1 regulates neurogenesis in the subventricular zone and promotes functional recovery after stroke
Galectin-1 regulates neurogenesis in the subventricular zone and promotes functional recovery after stroke
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DOI：
10.1016/j.expneurol.2007.06.024
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发表时间：
2007-10-01
影响因子：
5.3
通讯作者：
Mizusawa, Hidehiro
中科院分区：
文献类型：
--
作者：
Ishibashi, Satoru;Kuroiwa, Toshihiko;Mizusawa, Hidehiro
半乳糖凝集素-1(Galectin-1，Gal-1)是神经前体细胞增殖调控的关键分子，存在于侧脑室下区(SVZ)和海马齿状回颗粒下区。为了验证Gal-1参与成人局灶性脑缺血后神经发生的假说，我们在一个实验性的局灶性脑缺血模型上研究了内源性Gal-1表达的时间分布以及重组人Gal-I对神经发生和神经功能的影响。在正常脑组织中，Gal-1仅在SVZ区有表达。在缺血脑中，Gal-1在SVZ和纹状体梗塞周围选择性神经元死亡区域的表达明显上调。Gal-I表达的时间分布与缺血侧SVZ的神经前体细胞增殖相关。双标记研究表明Gal-1主要定位于反应性星形胶质细胞和SVZ星形胶质细胞。侧脑室注射已知具有碳水化合物结合能力的Gal-1可增加同侧SVZ的神经发生，并改善局灶性缺血后的感觉运动障碍。相反，用抗Gal-1中和抗体阻断SVZ内的Gal-1，强烈地抑制了神经发生，并降低了神经功能。这些结果提示，Gal-1通过其与糖结合的能力是成人SVZ神经发生的主要调节因子之一，并为Gal-1蛋白在改善卒中后感觉运动功能中的作用提供了证据。(C)2007 Elsevier Inc.保留所有权利。
Galectin-1 (Gal- 1) has recently been identified as a key molecule that plays important roles in the regulation of neural progenitor cell proliferation in two neurogenic regions: the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus. To test the hypothesis that Gal-1 contributes to adult neurogenesis after focal ischemia, we studied the temporal profile of endogenous Gal-1 expression and the effects of human recombinant Gal- I on neurogenesis and neurological functions in an experimental focal ischemic model. In the normal brain, Gal-1 expression was observed only in the SVZ. In the ischemic brain, Gal-1 expression was markedly upregulated in the SVZ and the area of selective neuronal death around the infarct in the striatum. The temporal profile of Gal- I expression was correlated with that of neural progenitor cell proliferation in the SVZ of the ischemic hemisphere. Double-labeling studies revealed that Gal-1 was localized predominantly in both reactive astrocytes and SVZ astrocytes. Administration of Gal-1, which is known to have carbohydrate-binding ability, into the lateral ventricle increased neurogenesis in the ipsilateral SVZ and improved sensorimotor dysfunction after focal ischemia. By contrast, blockade of Gal-1 in the SVZ by the administration of anti-Gal-1 neutralizing antibody strongly inhibited neurogenesis and diminished neurological function. These results suggest that Gal-1 is one of the principal regulators of adult SVZ neurogenesis through its carbohydrate-binding ability and provide evidence that Gal-1 protein has a role in the improvement of sensorimotor function after stroke. (C) 2007 Elsevier Inc. All rights reserved.