Lead exposure stimulates VEGF expression in the spinal cord and extends survival in a mouse model of ALS.
Lead exposure stimulates VEGF expression in the spinal cord and extends survival in a mouse model of ALS.
复制标题
DOI：
10.1016/j.nbd.2009.11.007
复制
发表时间：
2010-03
影响因子：
6.1
通讯作者：
Cassina P
中科院分区：
文献类型：
--
作者：
Barbeito AG;Martinez-Palma L;Vargas MR;Pehar M;Mañay N;Beckman JS;Barbeito L;Cassina P
环境铅暴露是肌萎缩侧索硬化症(ALS)的轻微危险因素，ALS是一种以运动神经元进行性退化为特征的瘫痪疾病。然而，最近的证据矛盾地表明，ALS患者的铅水平越高，存活时间越长。我们研究了低水平铅暴露对表达肌萎缩侧索硬化症相关超氧化物歧化酶-1G93A突变(SOD1G93A)小鼠存活的影响。暴露于铅的SOD1G93A小鼠存活时间更长，腹角血管内皮生长因子表达增加，星形胶质细胞减少。用低浓度、无毒的铅处理培养的SOD1G93A星形胶质细胞，可上调VEGF的表达，并显著减少共培养中运动神经元的丢失，这种作用可通过中和抗VEGF的抗体来阻止。铅对星形胶质细胞的作用可能解释了铅对SOD1G93A小鼠疾病进展的矛盾减缓和ALS患者生存的改善。了解铅是如何刺激星形胶质细胞产生血管内皮生长因子和减轻神经炎症的，可能会为治疗ALS提供一种新的治疗方法。
Exposure to environmental lead (Pb) is a mild risk factor for Amyotrophic Lateral Sclerosis (ALS), a paralytic disease characterized by progressive degeneration of motor neurons. However, recent evidence has paradoxically linked higher Pb levels in ALS patients with longer survival. We investigated the effects of low-level Pb exposure on survival of mice expressing the ALS-linked superoxide dismutase-1 G93A mutation (SOD1G93A). SOD1G93A mice exposed to Pb showed longer survival and increased expression of VEGF in the ventral horn associated with reduced astrocytosis. Pretreatment of cultured SOD1G93A astrocytes with low, non toxic Pb concentrations upregulated VEGF expression and significantly abrogated motor neuron loss in co-culture, an effect prevented by neutralizing antibodies to VEGF. The actions of Pb on astrocytes might explain its paradoxical slowing of disease progression in SOD1G93A mice and the improved survival of ALS patients. Understanding how Pb stimulates astrocytic VEGF production and reduces neuroinflammation may yield a new therapeutic approach for treating ALS.
登录
查看更多内容
影响因子：
10.4
作者：
Kosnett MJ;Wedeen RP;Rothenberg SJ;Hipkins KL;Materna BL;Schwartz BS;Hu H;Woolf A
通讯作者：
Woolf A
影响因子：
25
作者：
Nagai, Makiko;Re, Diane B.;Przedborski, Serge
通讯作者：
Przedborski, Serge
影响因子：
5.3
作者：
Cassina, Patricia;Cassina, Adriana;Radi, Rafael
通讯作者：
Radi, Rafael
影响因子：
10.4
作者：
Kamel, Freya;Umbach, David M.;Sandler, Dale P.
通讯作者：
Sandler, Dale P.
影响因子：
25
作者：
Storkebaum, E;Lambrechts, D;Carmeliet, P
通讯作者：
Carmeliet, P