Identification of a pro-elongation effect of diallyl disulfide, a major organosulfur compound in garlic oil, on microglial process
Identification of a pro-elongation effect of diallyl disulfide, a major organosulfur compound in garlic oil, on microglial process
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大蒜油中主要有机硫化合物二烯丙基二硫化物对小胶质细胞过程的促伸长作用的鉴定
DOI：
10.1016/j.jnutbio.2019.108323
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发表时间：
2020
影响因子：
5.6
通讯作者：
Chao Huang
中科院分区：
文献类型：
--
作者：
Xing Xu;Peili Hu;Yaoying Ma;Lijuan Tong;Dan Wang;Yue Wu;Zhuo Chen;Chao Huang
小胶质细胞是神经系统中的先天免疫细胞。在静息状态下，它们显示出分枝的形态，而在疾病刺激下，它们的过程将缩回，沿着促炎细胞因子的过度产生。逆转小胶质细胞过程收缩可能有助于减少促炎细胞因子的产生，并恢复小胶质细胞扫描周围环境的能力，使脑功能调节更加有效。我们发现，二烯丙基二硫化物（DADS），大蒜油中的主要有机硫化合物，在不同的剂量和时间点给药，促进小胶质细胞的过程中培养的系统和小鼠前额叶皮质的伸长以可逆的方式。脂多糖（LPS），一个经典的小胶质细胞激活剂，并没有影响在体外和体内条件下的DADS的这种促延长作用。功能研究显示，DADS预处理减弱了LPS诱导的小鼠培养的小胶质细胞和前额叶皮质中肿瘤坏死因子-α（TNF-α）和白细胞介素-1 β（IL-1β）mRNA水平的降低以及LPS诱导的IL-10和CD 206 mRNA水平的升高。蛋白激酶B（Akt）抑制可减弱DADS对小胶质细胞突起的促伸长作用，阻断DADS对LPS诱导的小鼠小胶质细胞和前额叶皮质炎症反应的调节作用。在神经炎症的体内模型中，DADS预处理防止LPS诱导的小鼠前额叶皮质中小胶质细胞突起的收缩，并在尾部悬挂测试和强迫游泳测试中减弱LPS诱导的不动时间增加。这些结果表明，DADS诱导Akt依赖性的小胶质细胞过程的延长，沿着抗炎表型的诱导。
Microglia are the innate immune cells in the nervous system. In the resting state, they display a ramified morphology, while upon disease stimulation their processes would be retracted, along with pro-inflammatory cytokine overproduction. Reversing microglial process retraction may help reduce pro-inflammatory cytokine production and restore microglia's ability to scan surrounding environments, rendering brain function regulation to be more effective. We found that diallyl disulfide (DADS), a major organosulfur compound in garlic oil, administered at different doses and time points, promoted microglial process elongation in both cultured systems and prefrontal cortexes in mice in a reversible manner. Lipopolysaccharide (LPS), a classical activator of microglia, did not affect this pro-elongation effect of DADS at conditions in vitro and in vivo. Functional studies revealed that DADS pre-treatment attenuated LPS-induced decreases in levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA as well as LPS-induced increases in levels of IL-10 and CD206 mRNA in both cultured microglia and prefrontal cortexes in mice. Protein kinase B (Akt) inhibition attenuated the pro-elongation effect of DADS on microglial process and blocked the regulatory effects of DADS on LPS-induced inflammatory responses in both cultured microglia and prefrontal cortexes in mice. In an in vivo model of neuroinflammation, DADS pre-treatment prevented LPS-induced retraction of microglial process in the prefrontal cortex in mice and attenuated LPS-induced increase in immobility time in the tail suspension test and forced swim test. These results indicate that DADS induces an Akt-dependent elongation of microglia process, along with the induction of an anti-inflammatory phenotype.