Moran Landhing M, McLaurin Kristen A, Booze Rosemarie M, Mactutus Charles F
Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina, Columbia, SC, United States.
Front Behav Neurosci. 2019 Aug 6;13:169. doi: 10.3389/fnbeh.2019.00169. eCollection 2019.
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 studies to elucidate the full potential and generalizability of phytoestrogen treatment for HAND.
在联合抗逆转录病毒疗法（cART）时代，人类免疫缺陷病毒1型（HIV-1）相关神经认知障碍（HAND）持续流行，且HIV-1血清反应阳性的老年个体患病率增加，因此迫切需要开发旨在保护和/或恢复神经认知功能的辅助治疗方法。为了填补这一知识空白，本研究考察了肠道微生物群产生的植物雌激素S-雌马酚（SE）作为一种创新治疗策略的效用。采用具有不同信号持续时间（1000、500、100毫秒）的信号检测操作性任务来评估HIV-1转基因（Tg）动物和对照动物的持续注意力。在信号检测预测试评估期间，与对照动物相比，HIV-1 Tg动物在刺激反应学习和持续注意力方面表现出严重缺陷。随后，在6至8月龄时，HIV-1 Tg动物和对照动物每天口服安慰剂或SE（0.05、0.1、0.2毫克），并在具有不同信号持续时间的信号检测操作性任务中进行后测试评估。在HIV-1 Tg动物中，随着SE剂量增加，观察到100毫秒时漏报次数呈线性下降，表明存在剂量反应，最有效剂量为0.2毫克SE，接近对照水平。比较预测试和后测试中不同信号持续时间的漏报次数发现，用0.2毫克SE治疗的HIV-1 Tg动物的神经认知功能得到了保留；这一效果与用安慰剂治疗的HIV-1 Tg动物中观察到的神经认知衰退形成鲜明对比。结果支持0.2毫克SE作为一种潜在有效的神经保护和/或神经恢复疗法，可用于HIV-1 Tg大鼠的持续注意力，且无任何外周不良反应。因此，本研究强调迫切需要进一步研究以阐明植物雌激素治疗HAND的全部潜力和普遍性。
