HIV-1 Tat and cocaine mediated synaptopathy in cortical and midbrain neurons is prevented by the isoflavone Equol

Bertrand, Sarah J.; Hu, Calvin; Aksenova, Marina; Mactutus, Charles F.; Booze, Rosemarie M.

doi:10.3389/fmicb.2015.00894

Cited by 23 publications

(36 citation statements)

References 76 publications

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“…Each rat was administered its treatment at least an hour after neurocognitive assessments and typically consumed their pellets within seconds. Animals were treated after neurocognitive assessments to promote long-term remodeling of neuronal circuitry by preventing synapse loss induced by HIV-1 viral proteins (e.g., Bertrand et al 2014Bertrand et al , 2015. Treatment was continued for 60 days.…”

Section: S-equolmentioning

confidence: 99%

“…Equol is an active metabolite produced by gut microbiota following the ingestion of the soy derived phytoestrogen DAI (Setchell et al 1984). S-Equol (SE), the only enantiomer produced by humans (Setchell et al 2005), exhibits neuroprotective effects via its selective affinity for ERβ (Setchell et al 2005;Bertrand et al 2015). Furthermore, when SE crosses the blood-brain-barrier it distributes most significantly to the prefrontal cortex (Lund et al 2001); a brain region associated with higher-order cognitive functioning.…”

Section: Introductionmentioning

confidence: 99%

“…Most critically, however, the translational relevance of SE is evidenced by its progression into clinical trials for Alzheimer's disease (Ausio Pharmaceuticls; NCT03101085), another progressive, neurodegenerative disorder. SE has been implicated as a potential adjunctive therapeutic for HAND in both in vitro (Bertrand et al 2015) and in vivo (Moran et al 2019) studies. In primary neuronal cell cultures, pretreatment with SE prevented synapse loss induced by the HIV-1 viral protein, Tat (Bertrand et al 2015).…”

Section: Introductionmentioning

confidence: 99%

“…SE has been implicated as a potential adjunctive therapeutic for HAND in both in vitro (Bertrand et al 2015) and in vivo (Moran et al 2019) studies. In primary neuronal cell cultures, pretreatment with SE prevented synapse loss induced by the HIV-1 viral protein, Tat (Bertrand et al 2015). Precursors to SE, including DAI and liquiritigenin (LQ), which also selectively target ERβ (DAI: Casanova et al 1999;LQ: Mersereau et al 2008), also prevented Tat induced neuronal apoptosis (Adams et al 2012) and restored synaptodendritic injury (Bertrand et al 2014).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Selective Estrogen Receptor β Agonists: a Therapeutic Approach for HIV-1 Associated Neurocognitive Disorders

McLaurin

Moran

Booze

et al. 2019

J Neuroimmune Pharmacol

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The persistence of HIV-1 associated neurocognitive disorders (HAND) in the post-cART era, afflicting between 40 and 70% of HIV-1 seropositive individuals, supports a critical need for the development of adjunctive therapeutic treatments. Selective estrogen receptor β agonists, including S-Equol (SE), have been implicated as potential therapeutic targets for the treatment of neurocognitive disorders. In the present study, the therapeutic efficacy of 0.2 mg SE for the treatment of HAND was assessed to address two key questions in the HIV-1 transgenic (Tg) rat. First, does SE exhibit robust therapeutic efficacy when treatment is initiated relatively early (i.e., between 2 and 3 months of age) in the course of viral protein exposure? Second, does the therapeutic utility of SE generalize across multiple neurocognitive domains? Treatment with SE enhanced preattentive processes and stimulus-response learning to the level of controls in all (i.e., 100%) HIV-1 Tg animals. For sustained and selective attention, statistically significant effects were not observed in the overall analyses (Control: Placebo, n = 10, SE, n = 10; HIV-1 Tg: Placebo, n = 10, SE, n = 10). However, given our a priori hypothesis, subsequent analyses were conducted, revealing enhanced sustained and selective attention, approximating controls, in a subset (i.e., 50%, n = 5 and 80%, n = 8, respectively) of HIV-1 Tg animals treated with SE. Thus, the therapeutic efficacy of SE is greater when treatment is initiated relatively early in the course of viral protein exposure and generalizes across neurocognitive domains, supporting an adjunctive therapeutic for HAND in the post-cART era.

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Section: S-equolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Selective Estrogen Receptor β Agonists: a Therapeutic Approach for HIV-1 Associated Neurocognitive Disorders

McLaurin

Moran

Booze

et al. 2019

J Neuroimmune Pharmacol

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“…Gp120, a structural viral gene product, is vital for viral entry into the CNS (Hao and Lyman, 1999) and may cause neurotoxicity by binding to cell surface receptors, ultimately leading to neuronal death (Lipton, 1991;Corasaniti et al, 2001a;Haughey and Mattson, 2002). Preclinical assessments, including both in vitro and in vivo studies, have extensively examined both Tat and gp120 (Brenneman et al, 1988;Lipton et al, 1995;Nath et al, 1996;Cheng et al, 1998;Aksenov et al, 2001;Corasaniti et al, 2001b;Bruce-Keller et al, 2003;Aksenova et al, 2006;Fitting et al, 2006a;Aksenov et al, 2008;Adams et al, 2010;Zhu et al, 2011;Bertrand et al, 2013;Fitting et al, 2013;Hahn et al, 2013;Bertrand et al, 2014Bertrand et al, , 2015Marks et al, 2016), providing strong evidence for the role of HIV-1 viral proteins in neurocognitive and neuroanatomical alterations in adulthood.…”

Section: Introductionmentioning

confidence: 99%

Dose‐dependent neurocognitive deficits following postnatal day 10 HIV‐1 viral protein exposure: Relationship to hippocampal anatomy parameters

Fitting

McLaurin

Booze

et al. 2017

Intl J of Devlp Neuroscience

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Despite the availability of antiretroviral prophylactic treatment, pediatric human immunodeficiency virus type 1 (HIV-1) continues to be a significant risk factor in the post-cART era. The time of infection (i.e., during pregnancy, delivery or breastfeeding) may play a role in the development of neurocognitive deficits in pediatric HIV-1. HIV-1 viral protein exposure on postnatal day (P)1, preceding the postnatal brain growth spurt in rats, had deleterious effects on neurocognitive development and anatomical parameters of the hippocampus (Fitting et al., 2008a,b). In the present study, rats were stereotaxically injected with HIV-1 viral proteins, including Tat and gp120, on P10 to further examine the role of timing on neurocognitive development and anatomical parameters of the hippocampus (Fitting et al., 2010). The dose-dependent virotoxin effects observed across development following P10 Tat exposure were specific to spatial learning and absent from prepulse inhibition and locomotor activity. A relationship between alterations in spatial learning and/or memory and hippocampal anatomical parameters was noted. Specifically, the estimated number of neurons and astrocytes in the hilus of the dentate gyrus explained 70% of the variance of search behavior in Morris water maze acquisition training for adolescents and 65% of the variance for adults; a brain-behavior relationship consistent with observations following P1 viral protein exposure. Collectively, late viral protein exposure (P10) results in selective alterations in neurocognitive development without modifying measures of somatic growth, preattentive processing, or locomotor activity, as characterized by early viral protein exposure (P1). Thus, timing may be a critical factor in disease progression, with children infected with HIV earlier in life being more vulnerable to CNS disease.

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The role of G-protein-coupled membrane estrogen receptor in mouse Leydig cell function—in vivo and in vitro evaluation

et al. 2018

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In this study, G-coupled estrogen receptor (GPER) was inactivated, by treatment with antagonist (G-15), in testes of C57BL/6 mice: immature (3 weeks old), mature (3 months old) and aged (1.5 years old) (50 μg/kg bw), as well as MA-10 mouse Leydig cells (10 nM/24 h) alone or in combination with 17β-estradiol or antiestrogen (ICI 182,780). In G-15-treated mice, overgrowth of interstitial tissue was found in both mature and aged testes. Depending on age, differences in structure and distribution of various Leydig cell organelles were observed. Concomitantly, modulation of activity of the mitochondria and tubulin microfibers was revealed. Diverse and complex GPER regulation at the mRNA level and protein of estrogen signaling molecules (estrogen receptor α and β; ERα, ERβ and cytochrome P450 aromatase; P450arom) in G-15 Leydig cells was found in relation to age and the experimental system utilized (in vivo and in vitro). Changes in expression patterns of ERs and P450arom, as well as steroid secretion, reflected Leydig cell heterogeneity to estrogen regulation throughout male life including cell physiological status.We show, for the first time, GPER with ERs and P450arom work in tandem to maintain Leydig cell architecture and supervise its steroidogenic function by estrogen during male life. Full set of estrogen signaling molecules, with involvement of GPER, is crucial for proper Leydig cell function where each molecule acts in a specific and/or complementary manner. Further understanding of the mechanisms by which GPER controls Leydig cells with special regard to male age, cell of origin and experimental system used is critical for predicting and preventing testis steroidogenic disorders based on perturbations in estrogen signaling.

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HIV-1 Tat and cocaine mediated synaptopathy in cortical and midbrain neurons is prevented by the isoflavone Equol

Cited by 23 publications

References 76 publications

Selective Estrogen Receptor β Agonists: a Therapeutic Approach for HIV-1 Associated Neurocognitive Disorders

Selective Estrogen Receptor β Agonists: a Therapeutic Approach for HIV-1 Associated Neurocognitive Disorders

Dose‐dependent neurocognitive deficits following postnatal day 10 HIV‐1 viral protein exposure: Relationship to hippocampal anatomy parameters

The role of G-protein-coupled membrane estrogen receptor in mouse Leydig cell function—in vivo and in vitro evaluation

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