Lead exposure stimulates VEGF expression in the spinal cord and extends survival in a mouse model of ALS

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• 作者：Ana G. Barbeito ; Laura Martinez-Palma ; Marcelo R. Vargas ; Mariana Pehar ; Nelly Mañ ; ay ; Joseph S. Beckman ; Luis Barbeito ; Patricia Cassina
• 关键词：Lead ; Amyotrophic lateral sclerosis ; SOD1^G93A ; VEGF ; Astrocytes
• 刊名：Neurobiology of Disease
• 出版年：2010
• 出版时间：March 2010
• 年：2010
• 卷：37
• 期：3
• 页码：574-580
• 全文大小：769 K

文摘

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 (SOD1^G93A). SOD1^G93A mice exposed to Pb showed longer survival and increased expression of VEGF in the ventral horn associated with reduced astrocytosis. Pretreatment of cultured SOD1^G93A astrocytes with low, non toxic Pb concentrations upregulated VEGF expression and significantly abrogated motor neuron loss in coculture, an effect prevented by neutralizing antibodies to VEGF. The actions of Pb on astrocytes might explain its paradoxical slowing of disease progression in SOD1^G93A 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.