Hydrogen sulfide (H2S) is a gaseous molecule found naturally in the environment, and as an industrial byproduct, and is known to cause acute death and induces long-term neurological disorders following acute high dose exposures. Currently, there is no drug approved for treatment of acute H2S-induced neurotoxicity and/or neurological sequelae. Lack of a deep understanding of pathogenesis of H2S-induced neurotoxicity has delayed the development of appropriate therapeutic drugs that target H2S-induced neuropathology. RNA sequencing analysis was performed to elucidate the cellular and molecular mechanisms of H2S-induced neurodegeneration, and to identify key molecular elements and pathways that contribute to H2S-induced neurotoxicity. C57BL/6J mice were exposed by whole body inhalation to 700 ppm of H2S for either one day, two consecutive days or 4 consecutive days. Magnetic resonance imaging (MRI) scan analyses showed H2S exposure induced lesions in the inferior colliculus (IC) and thalamus (TH). This mechanistic study focused on the IC. RNA Sequencing analysis revealed that mice exposed once, twice, or 4 times had 283, 193 and 296 differentially expressed genes (DEG), respectively (q-value < 0.05, fold-change> 1.5). Hydrogen sulfide exposure modulated multiple biological pathways including unfolded protein response, neurotransmitters, oxidative stress, hypoxia, calcium signaling, and inflammatory response in the IC. Hydrogen sulfide exposure activated PI3K/Akt and MAPK signaling pathways. Pro-inflammatory cytokines were shown to be potential initiators of the modulated signaling pathways following H2S exposure. Furthermore, microglia were shown to release IL-18 and astrocytes released both IL-1β and IL-18 in response to H2S. This transcriptomic analysis data revealed complex signaling pathways involved in H2S-induced neurotoxicity and may provide important associated mechanistic insights.

中文翻译：

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急性硫化氢暴露后脑下丘的转录组学分析。


硫化氢 (H2S) 是一种自然存在于环境中的气态分子，也是一种工业副产品，已知在急性高剂量接触后会导致急性死亡并诱发长期神经系统疾病。目前，还没有批准用于治疗 H2S 引起的急性神经毒性和/或神经系统后遗症的药物。由于缺乏对 H2S 诱导的神经毒性发病机制的深入了解，导致针对 H2S 诱导的神经病理学的适当治疗药物的开发受到阻碍。进行RNA测序分析是为了阐明H2S诱导的神经变性的细胞和分子机制，并确定导致H2S诱导的神经毒性的关键分子元件和途径。 C57BL/6J 小鼠通过全身吸入 700 ppm H2S 暴露一天、连续两天或连续 4 天。磁共振成像 (MRI) 扫描分析显示 H2S 暴露引起下丘 (IC) 和丘脑 (TH) 病变。本机制研究的重点是 IC。 RNA测序分析显示，暴露1次、2次或4次的小鼠分别有283、193和296个差异表达基因（DEG）（q值< 0.05，倍数变化> 1.5）。硫化氢暴露调节多种生物途径，包括未折叠蛋白反应、神经递质、氧化应激、缺氧、钙信号传导和 IC 中的炎症反应。硫化氢暴露激活 PI3K/Akt 和 MAPK 信号通路。促炎细胞因子被证明是 H2S 暴露后调节信号通路的潜在引发剂。此外，小胶质细胞响应 H2S 释放 IL-18，星形胶质细胞释放 IL-1β 和 IL-18。 该转录组分析数据揭示了 H2S 诱导的神经毒性中涉及的复杂信号通路，并可能提供重要的相关机制见解。