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Synaptodendritic recovery following HIV Tat exposure: neurorestoration by phytoestrogens.

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. 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.

SUBMITTER: Bertrand SJ

PROVIDER: S-EPMC4041987 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Synaptodendritic recovery following HIV Tat exposure: neurorestoration by phytoestrogens.

Bertrand Sarah J SJ Mactutus Charles F CF Aksenova Marina V MV Espensen-Sturges Tori D TD Booze Rosemarie M RM

Journal of neurochemistry 20130826 1

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 ...[more]

PMID: 23875777

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Project description:Due to the sustained prevalence of human immunodeficiency virus (HIV)-1 associated neurocognitive disorders (HAND) in the post-combination antiretroviral therapy (cART) era, as well as the increased prevalence of older HIV-1 seropositive individuals, there is a critical need to develop adjunctive therapeutics targeted at preserving and/or restoring neurocognitive function. To address this knowledge gap, the present study examined the utility of S-Equol (SE), a phytoestrogen produced by gut microbiota, as an innovative therapeutic strategy. A signal detection operant task with varying signal durations (1,000, 500, 100 ms) was utilized to assess sustained attention in HIV-1 transgenic (Tg) and control animals. During the signal detection pretest assessment, HIV-1 Tg animals displayed profound deficits in stimulus-response learning and sustained attention relative to control animals. Subsequently, between 6 and 8 months of age, HIV-1 Tg and control animals were treated with a daily oral dose of either placebo or SE (0.05, 0.1, 0.2 mg) and a posttest assessment was conducted in the signal detection operant task with varying signal durations. In HIV-1 Tg animals, a linear decrease in the number of misses at 100 ms was observed as SE dose increased, suggesting a dose response with the most effective dose at 0.2 mg SE, approximating controls. Comparison of the number of misses across signal durations at the pretest and posttest revealed a preservation of neurocognitive function in HIV-1 Tg animals treated with 0.2 mg SE; an effect that was in sharp contrast to the neurocognitive decline observed in HIV-1 Tg animals treated with placebo. The results support the utility of 0.2 mg SE as a potential efficacious neuroprotective and/or neurorestorative therapeutic for sustained attention, in the absence of any adverse peripheral effects, in the HIV-1 Tg rat. Thus, the present study highlights the critical need for further in vivo studies to elucidate the full potential and generalizability of phytoestrogen treatment for HAND.

Dataset Information

Synaptodendritic recovery following HIV Tat exposure: neurorestoration by phytoestrogens.

Publications

Synaptodendritic recovery following HIV Tat exposure: neurorestoration by phytoestrogens.

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