HIV-1 Tat介导的炎性因子持续存在和由其引发的星形胶质细胞异常活化参与HAND发生发展。嘌呤受体P2Y2R参与胶质细胞对神经元存活及功能调控。我们发现Tat可促进星形胶质细胞P2Y2R表达，但Tat上调P2Y2R表达的机制及其作用尚待探索。长链非编码RNA（lncRNA）是基因表达调控的新着眼点，我们发现lncRNA Gm14047与IL-1β反义链同源；Tat刺激的星形胶质细胞中Gm14047与P2Y2R表达同步上升，二者呈正相关。提示该lncRNA是P2Y2R的正调控因子，可调控P2Y2R表达影响神经元损伤。本项目拟应用慢病毒Tat制备的HAND模型，明确Gm14047在调控神经元损伤中的作用，从表观遗传学探索其调控P2Y2R表达机制，拓宽对P2Y2R的认识，深入解析HAND中神经元损伤的机理，为发展基于HAND发生发展的神经保护提供新策略和研发理想的治疗药物提供新靶点。

Human immunodeficiency virus type 1 (HIV-1) Tat, as a regulating protein, is essential for the pathogenesis of HIV-associated neurocognitive disorder (HAND) that is characterized by abnormal astrocytosis resulted from inflammatory factors. Accumulating reports show that purinergic P2Y2 receptor (P2Y2R) signaling plays a unique role in the neuron damage and function regulated by the astrocytes. Recently, our results indicate Tat can up-regulate P2Y2R expression both in primary astrocytes (in vitro) and the brain from Tat-induced HAND mice (in vivo). However, the mechanism and role of P2Y2R expression induced by Tat are less-known. The non-coding RNAs (lncRNAs) provide a new view of the gene expression regulation. Our studies represent that the lncRNA Gm14047 displays sequence similarity to antisense of IL-1 beta. Of importance, both the expression of Gm14047 and P2Y2R is up-regulated at the same time and display positive correlation in the astrocytes stimulated by Tat protein, which suggests that the lncRNA Gm14047 is a positive regulator of P2Y2R that has significantly effect on the neuron damage. In this project, we plan to elucidate the role of the lncRNA Gm14047 in regulation of the neuron damage and the regulation mechanism of P2Y2R expression from the epigenetics in HAND mice. If successful, this project will broaden our vision on the acknowledgements of P2Y2R signaling and the mechanism of the neuron damage in the HAND.