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

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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.

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Authors and Affiliations

  1. Laboratories of Cellular Neuroimmunology, University of Nebraska Medical Center, 68198-5215, Omaha, Nebraska, USA

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

  2. Neurotoxicology, Center for Neurovirology and Neurodegenerative Disorders, Department of Pharmacology, University of Nebraska Medical Center, 68198-5215, Omaha, Nebraska, USA

    Jialin Zheng

  3. Department of Pathology and Microbiology, University of Nebraska Medical Center, 68198-5215, Omaha, Nebraska, USA

    Jialin Zheng & Anuja Ghorpade

  4. Biochemistry and Molecular Biology, University of Nebraska Medical Center, 68198-5215, Omaha, Nebraska, USA

    Anuja Ghorpade

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  1. Muralidhar Deshpande
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  2. Jialin Zheng
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  3. Kathleen Borgmann
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  4. Raisa Persidsky
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  5. Li Wu
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  6. Courtney Schellpeper
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  7. Anuja Ghorpade
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Correspondence to Anuja Ghorpade.

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Deshpande, M., Zheng, J., Borgmann, K. et al. Role of activated astrocytes in neuronal damage: Potential links to HIV-1-associated dementia. neurotox res 7, 183–192 (2005). https://doi.org/10.1007/BF03036448

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  • DOI: https://doi.org/10.1007/BF03036448

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