Spatiotemporal analysis of signal transducer and activator of transcription 3 activation in rat brain astrocytes and pituitary following peripheral immune challenge

L. Gautron, P. Lafon, M. Chaigniau, G. Tramu, S. Layé

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

The host response to peripheral inflammation induces fever and behavioural depression that are supposed to be centrally mediated by cytokines. Several proinflammatory cytokines activate 'signal transducer and activator of transcription' 3 (STAT3) via gp130-like receptor signaling. In order to determine which cells in the rat brain and pituitary are activated during bacterial inflammation, we investigated in a spatiotemporal manner the activation of STAT3 in these organs following peripheral lipopolysaccharide (LPS) challenge. Under basal conditions, STAT3 immunoreactivity was observed in neurones and some glial cells throughout the brain. Two hours after the administration of LPS, nuclear localisation of STAT3 (hallmark of activation) was observed in zones at the interface between brain and blood or cerebrospinal fluid such as pituitary, ependymal layer, meninges, glia limitans, circumventricular organs and surrounding nervous parenchyma. Four hours after LPS, the nuclear activation of STAT3 propagated to cells located inside the parenchyma (cortex, hypothalamus, corpus callosum and hippocampus among others) and declined 8 h after treatment. Double labelling of STAT3 and glial fibrillary acidic protein identified activated cells in the parenchyma as astrocytes. These data show that STAT3 is activated in the pituitary and in brain astrocytes after a peripheral LPS challenge as demonstrated by immunohistochemistry. Astrocytes may therefore play a key role in the brain response to peripheral inflammation.

Original languageEnglish (US)
Pages (from-to)717-729
Number of pages13
JournalNeuroscience
Volume112
Issue number3
DOIs
StatePublished - Jul 5 2002

Keywords

  • Blood-brain barrier
  • Glia
  • Immunohistochemistry
  • Lipopolysaccharide
  • STAT3

ASJC Scopus subject areas

  • Neuroscience(all)

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