RNA deep sequencing analysis reveals that nicotine restores impaired gene expression by viral proteins in the brains of HIV-1 transgenic rats.
RNA deep sequencing analysis reveals that nicotine restores impaired gene expression by viral proteins in the brains of HIV-1 transgenic rats.
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DOI：
10.1371/journal.pone.0068517
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li MD
中科院分区：
文献类型：
--
作者：
Cao J;Wang S;Wang J;Cui W;Nesil T;Vigorito M;Chang SL;Li MD
尽管接受了高效抗逆转录病毒疗法，但感染HIV-1的人往往会发展成神经系统疾病。尽管潜在的机制在很大程度上尚未确定，但我们先前基于RNA-seq的研究表明，在HIV-1转基因（HIV-1 Tg）大鼠的中枢神经系统（CNS）中，许多基因的表达发生了改变。由于尼古丁是烟碱乙酰胆碱受体的天然激动剂，具有神经保护作用，我们目前测试了尼古丁恢复HIV-1 Tg大鼠CNS中改变基因表达的假设。成年雄性HIV-1 Tg和F344对照品系大鼠皮下注射尼古丁（0.25 mg/kg）或生理盐水，每天两次，持续17天。使用RNA深度测序技术评估前额叶皮层（PFC）、背侧海马（HIP）和背侧纹状体（STR）中的基因表达。我们发现，HIV-1 Tg大鼠中约20%的改变基因在每个大脑区域受到尼古丁的影响，其中大部分基因的表达得到恢复。对恢复基因的分析显示，尼古丁在HIV-1 Tg大鼠的不同脑区纠正了不同的途径。具体而言，两个最显着恢复的途径是PFC中的Wnt/β-catenin信号传导和ephrin B信号传导，HIP中的cAMP反应元件结合蛋白（CREB）信号传导和谷胱甘肽代谢途径，以及STR中的三羧酸（TCA）循环和钙信号传导。总之，我们的研究结果表明，胆碱能调节剂如尼古丁对HIV-1诱导的神经功能缺损具有有益作用。
Persons infected with HIV-1 often develop neurologic disorders despite receiving highly active anti-retroviral therapy. Although the underlying mechanism is largely undetermined, our previous RNA-seq-based study showed that the expression of many genes was altered in the central nervous system (CNS) of HIV-1 transgenic (HIV-1Tg) rats. Because nicotine, a natural agonist of nicotinic acetylcholine receptors, exhibits a neuroprotective effect, we presently tested the hypothesis that nicotine restores the expression of altered genes in the CNS of HIV-1Tg rats. Adult male HIV-1Tg and F344 control strain rats were injected with either nicotine (0.25 mg/kg) or saline subcutaneously twice a day for 17 days. Gene expression in the prefrontal cortex (PFC), dorsal hippocampus (HIP), and dorsal striatum (STR) was evaluated using the RNA deep sequencing technique. We found that about 20% of the altered genes in the HIV-1Tg rat were affected by nicotine in each brain region, with the expression of most restored. Analysis of the restored genes showed distinct pathways corrected by nicotine in different brain regions of HIV-1Tg rats. Specifically, the two most significantly restored pathways were Wnt/β-catenin signaling and ephrin B signaling in the PFC, cAMP-responsive element-binding protein (CREB) signaling and glutathione metabolism pathway in the HIP, and tricarboxylic acid (TCA) cycle and calcium signaling in the STR. Together, our findings indicate that cholinergic modulators such as nicotine have beneficial effects on HIV-1-induced neurologic deficits.
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影响因子：
9.8
作者：
Dieterich, Daniela C.;Karpova, Anna;Mikhaylova, Marina;Zdobnova, Irina;Koenig, Imbritt;Landwehr, Marco;Kreutz, Martin;Smalla, Karl-Heinz;Richter, Karin;Landgraf, Peter;Reissner, Carsten;Boeckers, Tobias M.;Zuschratter, Werner;Spilker, Christina;Seidenbecher, Constanze I.;Garner, Craig C.;Gundelfinger, Eckart D.;Kreutz, Michael R.
通讯作者：
Kreutz, Michael R.
影响因子：
9.3
作者：
De Simone R;Ajmone-Cat MA;Carnevale D;Minghetti L
通讯作者：
Minghetti L
影响因子：
2
作者：
Gilmartin, Marieke R.;Helmstetter, Fred J.
通讯作者：
Helmstetter, Fred J.
影响因子：
64.5
作者：
Dalva, MB;Takasu, MA;Greenberg, ME
通讯作者：
Greenberg, ME
DOI：
10.1017/s1461145710000179
发表时间：
2011-03-01
影响因子：
4.8
作者：
Cao, Junran;Dwyer, Jennifer B.;Li, Ming D.
通讯作者：
Li, Ming D.