Program in Behavioral Neuroscience Department of Psychology University of South Carolina Columbia, SC 29208, USA.
Sci Rep. 2016 Sep 6;6:32831. doi: 10.1038/srep32831.
The HIV-1 transgenic (Tg) rat, which expresses 7 of the 9 HIV-1 genes, was used to investigate the effect(s) of long-term HIV-1 viral protein exposure on chronic neurocognitive deficits observed in pediatric HIV-1 (PHIV). A longitudinal experimental design was used to assess the progression of temporal processing deficits, a potential underlying dimension of neurocognitive impairment in HIV-1. Gap prepulse inhibition (gap-PPI), a translational experimental paradigm, was conducted every thirty days from postnatal day (PD) 30 to PD 180. HIV-1 Tg animals, regardless of sex, displayed profound alterations in the development of temporal processing, assessed using prepulse inhibition. A differential sensitivity to the manipulation of interstimulus interval was observed in HIV-1 Tg animals in comparison to control animals. Moreover, presence of the HIV-1 transgene was diagnosed with 90.8% accuracy using measures of prepulse inhibition and temporal sensitivity. Progression of temporal processing deficits in the HIV-1 Tg rat affords a relatively untapped opportunity to increase our mechanistic understanding of the role of long-term exposure to HIV-1 viral proteins, observed in pediatric HIV-1, in the development of chronic neurological impairment, as well as suggesting an innovative clinical diagnostic screening tool.
HIV-1 转基因(Tg)大鼠表达了 9 种 HIV-1 基因中的 7 种,用于研究长期 HIV-1 病毒蛋白暴露对儿科 HIV-1(PHIV)中观察到的慢性神经认知缺陷的影响。采用纵向实验设计来评估时间处理缺陷的进展,这是 HIV-1 神经认知障碍的潜在潜在维度。间隙脉冲抑制(gap-PPI)是一种翻译实验范式,从出生后第 30 天(PD)至第 180 天,每隔 30 天进行一次。无论性别如何,HIV-1 Tg 动物在时间处理的发展方面均表现出明显的改变,这是通过脉冲抑制来评估的。与对照动物相比,HIV-1 Tg 动物对刺激间隔的操纵表现出不同的敏感性。此外,使用脉冲抑制和时间敏感性的测量,HIV-1 Tg 动物中 HIV-1 转基因的存在的诊断准确率达到 90.8%。HIV-1 Tg 大鼠的时间处理缺陷的进展为增加对长期暴露于 HIV-1 病毒蛋白在儿科 HIV-1 中观察到的慢性神经损伤发展中的作用的机制理解提供了相对未开发的机会,并提示了一种创新的临床诊断筛选工具。