Role of activated astrocytes in neuronal damage: Potential links to HIV-1-associated dementia

Muralidhar Deshpande, Jialin Zheng, Kathleen Borgmann, Raisa Persidsky, Li Wu, Courtney Schellpeper, Anuja Ghorpade

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

HIV-1-associated dementia (HAD) is an important complication of HIV-1 infection. Reactive astrogliosis is a key pathological feature in HAD brains and in other central nervous system (CNS) diseases. Activated astroglia may play a critical role in CNS inflammatory diseases such as HAD. In order to test the hypothesis that activated astrocytes cause neuronal injury, we stimulated primary human fetal astrocytes with HAD-relevant pro-inflammatory cytokine IL-1β. IL-1β-activated astrocytes induced apoptosis and significant changes in metabolic activity in primary human neurons. An FITC-conjugated pan-caspase inhibitor peptide FITC-VAD-FMK was used for confirming caspase activation in neurons. IL-1β activation enhanced the expression of death protein FasL in astrocytes, suggesting that FasL is one of the potential factors responsible for neurotoxicity observed in HAD and other CNS diseases involving glial inflammation. Our data presented here add to the developing picture of role of activated glia in HAD pathogenesis.

Original languageEnglish
Pages (from-to)183-192
Number of pages10
JournalNeurotoxicity Research
Volume7
Issue number3
DOIs
StatePublished - 1 Dec 2005

Keywords

  • Apoptosis
  • Astrocyte
  • Fas ligand (FasL)
  • Glial inflammation
  • HIV-1-associated dementia (HAD)
  • IL-1β activation
  • Neurodegeneration
  • Neurotoxicity

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