Neurotoxicity Research

, Volume 7, Issue 3, pp 183–192

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
Article

DOI: 10.1007/BF03036448

Cite this article as:
Deshpande, M., Zheng, J., Borgmann, K. et al. neurotox res (2005) 7: 183. doi:10.1007/BF03036448

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.

Keywords

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

Copyright information

© Springer 2005

Authors and Affiliations

  • Muralidhar Deshpande
    • 1
  • Jialin Zheng
    • 2
    • 3
  • Kathleen Borgmann
    • 1
  • Raisa Persidsky
    • 1
  • Li Wu
    • 1
  • Courtney Schellpeper
    • 1
  • Anuja Ghorpade
    • 1
    • 3
    • 4
  1. 1.Laboratories of Cellular NeuroimmunologyUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Neurotoxicology, Center for Neurovirology and Neurodegenerative Disorders, Department of PharmacologyUniversity of Nebraska Medical CenterOmahaUSA
  3. 3.Department of Pathology and MicrobiologyUniversity of Nebraska Medical CenterOmahaUSA
  4. 4.Biochemistry and Molecular BiologyUniversity of Nebraska Medical CenterOmahaUSA

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