Synaptodendritic recovery following HIV Tat exposure: Neurorestoration by phytoestrogens

Authors

  • Sarah J. Bertrand,

    1. Laboratory Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina, Columbia, South Carolina, USA
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  • Charles F. Mactutus,

    1. Laboratory Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina, Columbia, South Carolina, USA
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  • Marina V. Aksenova,

    1. Laboratory Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina, Columbia, South Carolina, USA
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  • Tori D. Espensen-Sturges,

    1. Laboratory Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina, Columbia, South Carolina, USA
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  • Rosemarie M. Booze

    Corresponding author
    1. Laboratory Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina, Columbia, South Carolina, USA
    • Address correspondence and reprint requests to Rosemarie M. Booze, Professor and Bicentennial Endowed Chair of Behavioral Neuroscience, Department of Psychology, 1512 Pendleton Street, Barnwell College Building, University of South Carolina, Columbia, SC 29208, USA. E-mail: booze@mailbox.sc.edu; booze@sc.edu

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Abstract

HIV-1 infects the brain and, despite antiretroviral therapy, many infected individuals suffer from HIV-1-associated neurocognitive disorders (HAND). HAND is associated with dendritic simplification and synaptic loss. Prevention of synaptodendritic damage may ameliorate or forestall neurocognitive decline in latent HIV-1 infections. The HIV-1 transactivating protein (Tat) is produced during viral latency in the brain and may cause synaptodendritic damage. This study examined the integrity of the dendritic network after exposure to HIV-1 Tat by labeling filamentous actin (F-actin)-rich structures (puncta) in primary neuronal cultures. After 24 h of treatment, HIV-1 Tat was associated with the dendritic arbor and produced a significant reduction of F-actin-labeled dendritic puncta as well as loss of dendrites. Pre-treatment with either of two plant-derived phytoestrogen compounds (daidzein and liquiritigenin), significantly reduced synaptodendritic damage following HIV-1 Tat treatment. In addition, 6 days after HIV-1 Tat treatment, treatment with either daidzein, or liquiritigenin enhanced recovery, via the estrogen receptor, from HIV-1 Tat-induced synaptodendritic damage. These results suggest that either liquiritigenin or daidzein may not only attenuate acute synaptodendritic injury in HIV-1 but may also promote recovery from synaptodendritic damage.

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The HIV-1 transactivating protein (Tat) is produced during viral latency in the brain. Treatment with either daidzein or liquiritigenin restored the loss of synaptic connectivity produced by HIV-1 Tat. This neurorestoration was mediated by estrogen receptors (ER). These results suggest that plant-derived phytoestrogens may promote recovery from HIV-1-induced synaptodendritic damage.

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