HIV-1 Tat and cocaine mediated synaptopathy in cortical and midbrain neurons is prevented by the isoflavone Equol.
HIV-1 Tat and cocaine mediated synaptopathy in cortical and midbrain neurons is prevented by the isoflavone Equol.
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DOI：
10.3389/fmicb.2015.00894
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发表时间：
2015
影响因子：
5.2
通讯作者：
Booze RM
中科院分区：
文献类型：
--
作者：
Bertrand SJ;Hu C;Aksenova MV;Mactutus CF;Booze RM
众所周知，可卡因等非法药物会增加艾滋病毒-1相关神经认知障碍(HAND)的可能性和严重性。在目前的研究中，在有或没有可卡因的情况下，暴露于低浓度的HIV-1病毒蛋白TAT 1-86B后，通过量化体外培养的神经元树突上丰富的丝状肌动蛋白(F-肌动蛋白)结构(即点状和树突)，评估了突触的完整性。此外，还测定了R-Equol(RE)或S-Equol(SE，大豆异黄酮衍生物，大豆苷元)对突触的保护作用。单独地，无论是低浓度的HIV-1Tat(10 NM)还是低浓度的可卡因(1.6μM)对F-肌动蛋白点状突触数均无显著影响；然而，同样低浓度的HIV-1Tat+可卡因联合使用显著减少了树突状突触。这种突触减少被RE或SE以雌激素受体β依赖的方式预先处理而被阻止。总之，SE的靶向治疗干预可以防止HIV-1+药物滥用的突触，从而潜在地影响手部的发育。
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.