Role of nitric oxide produced by iNOS through NF-κB pathway in migration of cerebellar granule neurons induced by Lipopolysaccharide

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• 作者：Daniela Arias-Salvatierra ; Ellen K. Silbergeld ; Leonor C. Acosta-Saavedra ; Emma S. Calderon-Ar ; a
• 关键词：NF-κ ; B ; LPS ; Nitric oxide ; Neuron ; Migration ; Brain development
• 刊名：Cellular Signalling
• 出版年：2011
• 出版时间：February 2011
• 年：2011
• 卷：23
• 期：2
• 页码：425-435
• 全文大小：1830 K

文摘

Inflammatory stimulus during development increases the risk for adverse neurologic outcome. One possible mechanism is disrupting neuronal migration. Using lipopolysaccharide (LPS)-treatment to assess inflammatory stimulus on neuronal migration of cerebellar granule neurons, we previously found that LPS-activation increased the neuronal migration. The precise mechanisms behind these effects have not been investigated.

Independently, it was shown that nitric oxide (NO^•−) regulates neuronal migration during development, that NO^•– is produced by inducible nitric oxide synthase (iNOS) in response to LPS through the activation of nuclear factor (NF)-κB, and that LPS induce the expression of genes under the transcriptional control of NF-κB in primary cultures from developing mouse cerebellum. To investigate the relationship between these events, we used this culture model to study the role of NO^•– produced by iNOS through NF-κB signaling pathway, in the effect of LPS on neuron migration.

LPS increased NO^•– production, iNOS protein levels and NF-κB nuclear levels; concomitantly with NO^•– production, LPS increased the neuronal migration as compared to non stimulated cultures. The necessary roles of the NO^•– and iNOS were demonstrated by chelating of NO^•– with hemoglobin and the inhibition of iNOS by 1400 W. Each of these treatments reduced neuronal migration induced by LPS. The role of NF-κB was showed by using the inhibitor JSH-23, which decreased NO^•– production and neuronal migration in LPS activated cultures. These results suggest that neuronal migration during development is susceptible to be modified by pro-inflammatory stimulus such as LPS through intracellular pathways associated with their receptors.