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

Daniela Arias-Salvatierra, Ellen K. Silbergeld, Leonor C. Acosta-Saavedra, Emma S. Calderon-Aranda

Research output: Contribution to journalArticlepeer-review

Abstract

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 1400W. 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.

Original languageEnglish (US)
Pages (from-to)425-435
Number of pages11
JournalCellular Signalling
Volume23
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • Brain development
  • LPS
  • Migration
  • NF-κB
  • Neuron
  • Nitric oxide

ASJC Scopus subject areas

  • Cell Biology

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