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

Bertrand SJ, Hu C, Aksenova MV, Mactutus CF, Booze RM - Front Microbiol (2015)

Bottom Line: In addition, the synapse-protective effects of either R-Equol (RE) or S-Equol (SE; derivatives of the soy isoflavone, daidzein) were determined.Individually, neither low concentrations of HIV-1 Tat (10 nM) nor low concentrations of cocaine (1.6 μM) had any significant effect on F-actin puncta number; however, the same low concentrations of HIV-1 Tat + cocaine in combination significantly reduced dendritic synapses.This synaptic reduction was prevented by pre-treatment with either RE or SE, in an estrogen receptor beta dependent manner.

View Article: PubMed Central - PubMed

Affiliation: Laboratory Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina Columbia, SC, USA.

ABSTRACT
Illicit drugs, such as cocaine, are known to increase the likelihood and severity of HIV-1 associated neurocognitive disorders (HAND). In the current studies synaptic integrity was assessed following exposure to low concentrations of the HIV-1 viral protein Tat 1-86B, with or without cocaine, by quantifying filamentous actin (F-actin) rich structures (i.e., puncta and dendritic spines) on neuronal dendrites in vitro. In addition, the synapse-protective effects of either R-Equol (RE) or S-Equol (SE; derivatives of the soy isoflavone, daidzein) were determined. Individually, neither low concentrations of HIV-1 Tat (10 nM) nor low concentrations of cocaine (1.6 μM) had any significant effect on F-actin puncta number; however, the same low concentrations of HIV-1 Tat + cocaine in combination significantly reduced dendritic synapses. This synaptic reduction was prevented by pre-treatment with either RE or SE, in an estrogen receptor beta dependent manner. In sum, targeted therapeutic intervention with SE may prevent HIV-1 + drug abuse synaptopathy, and thereby potentially influence the development of HAND.

No MeSH data available.


Related in: MedlinePlus

R-Equol (RE) and S-Equol (SE) prevented synaptic loss induced by HIV-1 Tat (50 nM) via an estrogen receptor mediated mechanism. (A) Conversion of the soy isoflavone daidzein to SE. The dotted circle identifies a chiral center on carbon 3 wherein a conformational change produces RE. However, only SE may be produced by mammalian gut bacteria. (B) A moderate concentration of RE (50 nM), but not a low concentration (33 nM), prevented significant F-actin puncta loss induced by HIV-1 Tat (50 nM; p ≤ 0.01). (C) Both the low (33 nM) and moderate (50 nM) concentrations of SE prevented HIV-1 Tat induced F-actin puncta loss (p ≤ 0.05 and p ≤ 0.001, respectively). (D) 1 h pre-treatment with TMX (100 nM) blocked the protective effects of RE and SE (50 nM) against HIV-1 Tat (50 nM) in midbrain neurons. Mean ± SEM, ∗p ≤ 0.05 compared to HIV-1 Tat treatment.
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Figure 1: R-Equol (RE) and S-Equol (SE) prevented synaptic loss induced by HIV-1 Tat (50 nM) via an estrogen receptor mediated mechanism. (A) Conversion of the soy isoflavone daidzein to SE. The dotted circle identifies a chiral center on carbon 3 wherein a conformational change produces RE. However, only SE may be produced by mammalian gut bacteria. (B) A moderate concentration of RE (50 nM), but not a low concentration (33 nM), prevented significant F-actin puncta loss induced by HIV-1 Tat (50 nM; p ≤ 0.01). (C) Both the low (33 nM) and moderate (50 nM) concentrations of SE prevented HIV-1 Tat induced F-actin puncta loss (p ≤ 0.05 and p ≤ 0.001, respectively). (D) 1 h pre-treatment with TMX (100 nM) blocked the protective effects of RE and SE (50 nM) against HIV-1 Tat (50 nM) in midbrain neurons. Mean ± SEM, ∗p ≤ 0.05 compared to HIV-1 Tat treatment.

Mentions: Midbrain neurons were pre-treated with either RE (33 or 50 nM) or SE (33 or 50 nM) for 24 h prior to 50 nM HIV-1 Tat (Figure 1). There was a significant main effect of treatment F(1,22) = 9.4, p ≤ 0.001, with 50 nM HIV-1 Tat producing a significant reduction in F-actin puncta (p ≤ 0.001). Pre-treatment with 50 nM RE (p ≤ 0.01), but not 33 nM RE, prevented significant loss of F-actin puncta following 50 nM HIV-1 Tat (Figure 1B). Pre-treatment with either 33 nM SE (p ≤ 0.05) or 50 nM SE (p ≤ 0.001) prevented HIV-1 Tat induced loss of F-actin puncta (Figure 1C). RE and SE treatment alone did not produce either significant loss or proliferation of F-actin puncta (Figures 1B,C). RE or SE pre-treated HIV-1 Tat (50 nM) neurons were not statistically different from vehicle-treated neurons.


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

Bertrand SJ, Hu C, Aksenova MV, Mactutus CF, Booze RM - Front Microbiol (2015)

R-Equol (RE) and S-Equol (SE) prevented synaptic loss induced by HIV-1 Tat (50 nM) via an estrogen receptor mediated mechanism. (A) Conversion of the soy isoflavone daidzein to SE. The dotted circle identifies a chiral center on carbon 3 wherein a conformational change produces RE. However, only SE may be produced by mammalian gut bacteria. (B) A moderate concentration of RE (50 nM), but not a low concentration (33 nM), prevented significant F-actin puncta loss induced by HIV-1 Tat (50 nM; p ≤ 0.01). (C) Both the low (33 nM) and moderate (50 nM) concentrations of SE prevented HIV-1 Tat induced F-actin puncta loss (p ≤ 0.05 and p ≤ 0.001, respectively). (D) 1 h pre-treatment with TMX (100 nM) blocked the protective effects of RE and SE (50 nM) against HIV-1 Tat (50 nM) in midbrain neurons. Mean ± SEM, ∗p ≤ 0.05 compared to HIV-1 Tat treatment.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561964&req=5

Figure 1: R-Equol (RE) and S-Equol (SE) prevented synaptic loss induced by HIV-1 Tat (50 nM) via an estrogen receptor mediated mechanism. (A) Conversion of the soy isoflavone daidzein to SE. The dotted circle identifies a chiral center on carbon 3 wherein a conformational change produces RE. However, only SE may be produced by mammalian gut bacteria. (B) A moderate concentration of RE (50 nM), but not a low concentration (33 nM), prevented significant F-actin puncta loss induced by HIV-1 Tat (50 nM; p ≤ 0.01). (C) Both the low (33 nM) and moderate (50 nM) concentrations of SE prevented HIV-1 Tat induced F-actin puncta loss (p ≤ 0.05 and p ≤ 0.001, respectively). (D) 1 h pre-treatment with TMX (100 nM) blocked the protective effects of RE and SE (50 nM) against HIV-1 Tat (50 nM) in midbrain neurons. Mean ± SEM, ∗p ≤ 0.05 compared to HIV-1 Tat treatment.
Mentions: Midbrain neurons were pre-treated with either RE (33 or 50 nM) or SE (33 or 50 nM) for 24 h prior to 50 nM HIV-1 Tat (Figure 1). There was a significant main effect of treatment F(1,22) = 9.4, p ≤ 0.001, with 50 nM HIV-1 Tat producing a significant reduction in F-actin puncta (p ≤ 0.001). Pre-treatment with 50 nM RE (p ≤ 0.01), but not 33 nM RE, prevented significant loss of F-actin puncta following 50 nM HIV-1 Tat (Figure 1B). Pre-treatment with either 33 nM SE (p ≤ 0.05) or 50 nM SE (p ≤ 0.001) prevented HIV-1 Tat induced loss of F-actin puncta (Figure 1C). RE and SE treatment alone did not produce either significant loss or proliferation of F-actin puncta (Figures 1B,C). RE or SE pre-treated HIV-1 Tat (50 nM) neurons were not statistically different from vehicle-treated neurons.

Bottom Line: In addition, the synapse-protective effects of either R-Equol (RE) or S-Equol (SE; derivatives of the soy isoflavone, daidzein) were determined.Individually, neither low concentrations of HIV-1 Tat (10 nM) nor low concentrations of cocaine (1.6 μM) had any significant effect on F-actin puncta number; however, the same low concentrations of HIV-1 Tat + cocaine in combination significantly reduced dendritic synapses.This synaptic reduction was prevented by pre-treatment with either RE or SE, in an estrogen receptor beta dependent manner.

View Article: PubMed Central - PubMed

Affiliation: Laboratory Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina Columbia, SC, USA.

ABSTRACT
Illicit drugs, such as cocaine, are known to increase the likelihood and severity of HIV-1 associated neurocognitive disorders (HAND). In the current studies synaptic integrity was assessed following exposure to low concentrations of the HIV-1 viral protein Tat 1-86B, with or without cocaine, by quantifying filamentous actin (F-actin) rich structures (i.e., puncta and dendritic spines) on neuronal dendrites in vitro. In addition, the synapse-protective effects of either R-Equol (RE) or S-Equol (SE; derivatives of the soy isoflavone, daidzein) were determined. Individually, neither low concentrations of HIV-1 Tat (10 nM) nor low concentrations of cocaine (1.6 μM) had any significant effect on F-actin puncta number; however, the same low concentrations of HIV-1 Tat + cocaine in combination significantly reduced dendritic synapses. This synaptic reduction was prevented by pre-treatment with either RE or SE, in an estrogen receptor beta dependent manner. In sum, targeted therapeutic intervention with SE may prevent HIV-1 + drug abuse synaptopathy, and thereby potentially influence the development of HAND.

No MeSH data available.


Related in: MedlinePlus