Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration

Toyoko Arimoto, Guoying Bing

Research output: Contribution to journalArticlepeer-review

170 Scopus citations

Abstract

The present study was designed to examine whether expression of iNOS was involved in LPS-induced neurodegeneration in rat substantia nigra (SN) and to study the role of NO in the loss of the SN dopaminergic neurons. In Western blot analysis, iNOS was induced in the SN after injection of LPS in a time- and dose-dependent manner. Immunofluorescence and immunohistochemical analyses revealed that the iNOS is located in a fully activated microglia with the characteristic amoeboid morphology. Furthermore, LPS-induced loss of dopaminergic neurons was significantly inhibited by the administration of L-NG-nitroarginine, a selective inhibitor of NOS, and the glucocorticoid dexamethasone. These inhibiting agents for iNOS reduced LPS-induced microglial activation, suggesting that NO has a role in inflammatory-mediated microglial activation. These results demonstrate that LPS induces the expression of iNOS in activated microglia in the SN, and that NO and/or its metabolites may play a crucial role in inflammation-mediated degeneration of dopaminergic neurons.

Original languageEnglish
Pages (from-to)35-45
Number of pages11
JournalNeurobiology of Disease
Volume12
Issue number1
DOIs
StatePublished - Feb 2003

Bibliographical note

Funding Information:
We gratefully acknowledge Sarah Kennedy for her immunohistochemistry technical assistance and Xuan Nguyen for his computer technical assistance, as well as Dr. Robert Lasley for help with the NO analyzer. This work was supported by a grant from NIH (NS 39345 to G.B.).

Keywords

  • Inducible nitric oxide synthase
  • Inflammation
  • Lipopolysaccharide
  • Microglia
  • Neurodegeneration
  • Nitric oxide

ASJC Scopus subject areas

  • Neurology

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