Limits...
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

HIV-1 Tat (10 nM) + cocaine (1.6 μM) treatment produced significant synaptic loss in midbrain and cortical neurons, which was prevented by pre-treatment with either RE or SE. (A) Treatment with either SE, RE, HIV-1 Tat, or cocaine does not significantly alter the density of dendritic F-actin puncta compared to controls in midbrain neurons. Treatment with HIV-1 Tat + cocaine produced significant loss of F-actin puncta (p ≤ 0.05). (B) Treatment with either SE, RE, HIV-1 Tat, or cocaine does not significantly alter the density of dendritic F-actin puncta compared to controls in cortical neurons. Treatment with HIV-1 Tat + cocaine produced significant loss of F-actin puncta (p ≤ 0.05). (C) Pre-treatment with either RE or SE (50 nM) prevented dendritic F-actin puncta loss caused by HIV-1 Tat + cocaine treatments in midbrain neurons. Dendrites from pre-treated neurons are not significantly different from vehicle-treated controls (mean values, dotted line). (D) Pre-treatment with either RE or SE (50 nM) prevents HIV-1Tat + cocaine induced loss of dendritic F-actin puncta (p ≤ 0.001) in cortical neurons. Dendrites from pre-treated neurons are not significantly different from vehicle-treated controls (mean values, dotted line). (E) Pre-treatment of midbrain neurons with TMX (100 nM) for 1 h prior to either RE or SE prevented the protective effects of RE and SE, suggesting an estrogen receptor mediated mechanism. Vehicle-treated control mean values are represented by dotted line. (F) Pre-treatment of cortical neurons with TMX (100 nM) for 1 h prior to either RE or SE prevented the protective effects of RE and SE, suggesting an estrogen receptor mediated mechanism. Control mean value represented by dotted line. Mean ± SEM, ∗p ≤ 0.05 compared either to vehicle-treated controls (A,B) or HIV-1 Tat + cocaine (C,D).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4561964&req=5

Figure 2: HIV-1 Tat (10 nM) + cocaine (1.6 μM) treatment produced significant synaptic loss in midbrain and cortical neurons, which was prevented by pre-treatment with either RE or SE. (A) Treatment with either SE, RE, HIV-1 Tat, or cocaine does not significantly alter the density of dendritic F-actin puncta compared to controls in midbrain neurons. Treatment with HIV-1 Tat + cocaine produced significant loss of F-actin puncta (p ≤ 0.05). (B) Treatment with either SE, RE, HIV-1 Tat, or cocaine does not significantly alter the density of dendritic F-actin puncta compared to controls in cortical neurons. Treatment with HIV-1 Tat + cocaine produced significant loss of F-actin puncta (p ≤ 0.05). (C) Pre-treatment with either RE or SE (50 nM) prevented dendritic F-actin puncta loss caused by HIV-1 Tat + cocaine treatments in midbrain neurons. Dendrites from pre-treated neurons are not significantly different from vehicle-treated controls (mean values, dotted line). (D) Pre-treatment with either RE or SE (50 nM) prevents HIV-1Tat + cocaine induced loss of dendritic F-actin puncta (p ≤ 0.001) in cortical neurons. Dendrites from pre-treated neurons are not significantly different from vehicle-treated controls (mean values, dotted line). (E) Pre-treatment of midbrain neurons with TMX (100 nM) for 1 h prior to either RE or SE prevented the protective effects of RE and SE, suggesting an estrogen receptor mediated mechanism. Vehicle-treated control mean values are represented by dotted line. (F) Pre-treatment of cortical neurons with TMX (100 nM) for 1 h prior to either RE or SE prevented the protective effects of RE and SE, suggesting an estrogen receptor mediated mechanism. Control mean value represented by dotted line. Mean ± SEM, ∗p ≤ 0.05 compared either to vehicle-treated controls (A,B) or HIV-1 Tat + cocaine (C,D).

Mentions: In order to examine the effects of HIV-1 Tat and cocaine on F-actin puncta, a low dose of HIV-1 Tat 1–86 (10 nM) and a physiologically relevant dose of cocaine (1.6 μM) were simultaneously added to the cultures and incubated for 24 h. As shown in Figures 2A,B, there was a significant effect of HIV-1 Tat + cocaine F(1,123) = 16.4, (p ≤ 0.001) but no significant effect of either HIV-1 Tat or cocaine individually on dendritic F-actin puncta. Neurons cultured from fetal cortical and midbrain regions responded to HIV-1 Tat + cocaine similarly, as there were no significant differences between the brain region cultured F(1,123) = 3.4, p > 0.05.


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)

HIV-1 Tat (10 nM) + cocaine (1.6 μM) treatment produced significant synaptic loss in midbrain and cortical neurons, which was prevented by pre-treatment with either RE or SE. (A) Treatment with either SE, RE, HIV-1 Tat, or cocaine does not significantly alter the density of dendritic F-actin puncta compared to controls in midbrain neurons. Treatment with HIV-1 Tat + cocaine produced significant loss of F-actin puncta (p ≤ 0.05). (B) Treatment with either SE, RE, HIV-1 Tat, or cocaine does not significantly alter the density of dendritic F-actin puncta compared to controls in cortical neurons. Treatment with HIV-1 Tat + cocaine produced significant loss of F-actin puncta (p ≤ 0.05). (C) Pre-treatment with either RE or SE (50 nM) prevented dendritic F-actin puncta loss caused by HIV-1 Tat + cocaine treatments in midbrain neurons. Dendrites from pre-treated neurons are not significantly different from vehicle-treated controls (mean values, dotted line). (D) Pre-treatment with either RE or SE (50 nM) prevents HIV-1Tat + cocaine induced loss of dendritic F-actin puncta (p ≤ 0.001) in cortical neurons. Dendrites from pre-treated neurons are not significantly different from vehicle-treated controls (mean values, dotted line). (E) Pre-treatment of midbrain neurons with TMX (100 nM) for 1 h prior to either RE or SE prevented the protective effects of RE and SE, suggesting an estrogen receptor mediated mechanism. Vehicle-treated control mean values are represented by dotted line. (F) Pre-treatment of cortical neurons with TMX (100 nM) for 1 h prior to either RE or SE prevented the protective effects of RE and SE, suggesting an estrogen receptor mediated mechanism. Control mean value represented by dotted line. Mean ± SEM, ∗p ≤ 0.05 compared either to vehicle-treated controls (A,B) or HIV-1 Tat + cocaine (C,D).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: HIV-1 Tat (10 nM) + cocaine (1.6 μM) treatment produced significant synaptic loss in midbrain and cortical neurons, which was prevented by pre-treatment with either RE or SE. (A) Treatment with either SE, RE, HIV-1 Tat, or cocaine does not significantly alter the density of dendritic F-actin puncta compared to controls in midbrain neurons. Treatment with HIV-1 Tat + cocaine produced significant loss of F-actin puncta (p ≤ 0.05). (B) Treatment with either SE, RE, HIV-1 Tat, or cocaine does not significantly alter the density of dendritic F-actin puncta compared to controls in cortical neurons. Treatment with HIV-1 Tat + cocaine produced significant loss of F-actin puncta (p ≤ 0.05). (C) Pre-treatment with either RE or SE (50 nM) prevented dendritic F-actin puncta loss caused by HIV-1 Tat + cocaine treatments in midbrain neurons. Dendrites from pre-treated neurons are not significantly different from vehicle-treated controls (mean values, dotted line). (D) Pre-treatment with either RE or SE (50 nM) prevents HIV-1Tat + cocaine induced loss of dendritic F-actin puncta (p ≤ 0.001) in cortical neurons. Dendrites from pre-treated neurons are not significantly different from vehicle-treated controls (mean values, dotted line). (E) Pre-treatment of midbrain neurons with TMX (100 nM) for 1 h prior to either RE or SE prevented the protective effects of RE and SE, suggesting an estrogen receptor mediated mechanism. Vehicle-treated control mean values are represented by dotted line. (F) Pre-treatment of cortical neurons with TMX (100 nM) for 1 h prior to either RE or SE prevented the protective effects of RE and SE, suggesting an estrogen receptor mediated mechanism. Control mean value represented by dotted line. Mean ± SEM, ∗p ≤ 0.05 compared either to vehicle-treated controls (A,B) or HIV-1 Tat + cocaine (C,D).
Mentions: In order to examine the effects of HIV-1 Tat and cocaine on F-actin puncta, a low dose of HIV-1 Tat 1–86 (10 nM) and a physiologically relevant dose of cocaine (1.6 μM) were simultaneously added to the cultures and incubated for 24 h. As shown in Figures 2A,B, there was a significant effect of HIV-1 Tat + cocaine F(1,123) = 16.4, (p ≤ 0.001) but no significant effect of either HIV-1 Tat or cocaine individually on dendritic F-actin puncta. Neurons cultured from fetal cortical and midbrain regions responded to HIV-1 Tat + cocaine similarly, as there were no significant differences between the brain region cultured F(1,123) = 3.4, p > 0.05.

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