Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina, 1512 Pendleton Street, Columbia, SC, 29208, USA.
J Neurovirol. 2020 Oct;26(5):704-718. doi: 10.1007/s13365-020-00886-5. Epub 2020 Sep 1.
Chronic neurocognitive impairments, commonly associated with pediatric human immunodeficiency virus type 1 (PHIV), are a detrimental consequence of early exposure to HIV-1 viral proteins. Strong evidence supports S-Equol (SE) as an efficacious adjunctive neuroprotective and/or neurorestorative therapeutic for neurocognitive impairments in adult ovariectomized female HIV-1 transgenic (Tg) rats. There remains, however, a critical need to assess the therapeutic efficacy of SE when treatment occurs at an earlier age (i.e., resembling a therapeutic for children with PHIV) and across the factor of biological sex. Utilization of a series of signal detection operant tasks revealed prominent, sex-dependent neurocognitive deficits in the HIV-1 Tg rat, characterized by alterations in stimulus-reinforcement learning, the response profile, and temporal processing. Early (i.e., postnatal day 28) initiation of SE treatment precluded the development of chronic neurocognitive impairments in all (i.e., 100%) HIV-1 Tg animals, albeit not for all neurocognitive domains. Most notably, the therapeutic effects of SE are generalized across the factor of biological sex, despite the presence of endogenous hormones. Results support, therefore, the efficacy of SE as a neuroprotective therapeutic for chronic neurocognitive impairments in the post-cART era; an adjunctive therapeutic that demonstrates high efficacy in both males and females. Optimizing treatment conditions by evaluating multiple factors (i.e., age, neurocognitive domains, and biological sex) associated with PHIV and HIV-1 associated neurocognitive disorders (HAND) affords a key opportunity to improve the therapeutic efficacy of SE.
慢性神经认知障碍，通常与儿科人类免疫缺陷病毒 1 型（PHIV）相关，是早期暴露于 HIV-1 病毒蛋白的有害后果。强有力的证据支持 S-Equol（SE）作为一种有效的辅助神经保护和/或神经修复治疗，用于治疗成年去卵巢雌性 HIV-1 转基因（Tg）大鼠的神经认知障碍。然而，仍然需要评估 SE 的治疗效果，特别是在更早的年龄（即类似于 PHIV 儿童的治疗）和生物学性别因素方面。利用一系列信号检测操作性任务，发现 HIV-1 Tg 大鼠存在显著的性别依赖神经认知缺陷，其特征为刺激-强化学习、反应模式和时间处理的改变。早期（即出生后第 28 天）开始 SE 治疗可防止所有（即 100%）HIV-1 Tg 动物发生慢性神经认知障碍，但并非所有神经认知领域均如此。值得注意的是，SE 的治疗效果在生物学性别因素上具有普遍性，尽管存在内源性激素。因此，SE 作为一种治疗慢性神经认知障碍的神经保护治疗药物具有疗效，在男性和女性中均具有高效性。通过评估与 PHIV 和 HIV-1 相关的神经认知障碍（HAND）相关的多个因素（即年龄、神经认知领域和生物学性别），优化治疗条件，为提高 SE 的治疗效果提供了一个关键机会。
