Department of Physiology and Pharmacology, "La Sapienza" University of Rome, Rome, Italy.
Department of Clinical Medicine and Surgery, Section of Gastroenterology, University of Naples "Federico II", Naples, Italy.
Sci Rep. 2017 Aug 10;7(1):7735. doi: 10.1038/s41598-017-05245-9.
Despite the effectiveness of combined anti-retroviral therapy, human immunodeficiency virus (HIV) infected-patients frequently report diarrhea and neuropsychological deficits. It is claimed that the viral HIV-1 Trans activating factor (HIV-1 Tat) protein is responsible for both diarrhea and neurotoxic effects, but the underlying mechanisms are not known. We hypothesize that colonic application of HIV-1 Tat activates glial cells of the enteric nervous system (EGCs), leading to a neuroinflammatory response able to propagate to the central nervous system. We demonstrated that HIV-1 Tat-induced diarrhea was associated with a significant activation of glial cells within the colonic wall, the spinal cord and the frontal cortex, and caused a consistent impairment of the cognitive performances. The inhibition of glial cells activity by lidocaine, completely abolished the above-described effects. These observations point out the role of glial cells as putative effectors in HIV-1 Tat-associated gastrointestinal and neurological manifestations and key regulators of gut-brain signaling.
尽管联合抗逆转录病毒疗法有效,但人类免疫缺陷病毒 (HIV) 感染患者经常报告腹泻和神经心理缺陷。据称,病毒 HIV-1 转录激活因子 (HIV-1 Tat) 蛋白是导致腹泻和神经毒性作用的原因,但潜在机制尚不清楚。我们假设,HIV-1 Tat 在结肠中的应用会激活肠神经系统 (EGC) 的神经胶质细胞,导致能够传播到中枢神经系统的神经炎症反应。我们证明,HIV-1 Tat 诱导的腹泻与结肠壁、脊髓和额叶皮层内神经胶质细胞的显著激活有关,并导致认知表现持续受损。利多卡因抑制神经胶质细胞的活性,完全消除了上述作用。这些观察结果指出了神经胶质细胞作为 HIV-1 Tat 相关胃肠道和神经表现的潜在效应物以及肠道-大脑信号转导的关键调节剂的作用。