Graduate Institute of Food Safety, College of Agriculture and Natural Resources, National Chung Hsing University, Taichung 402, Taiwan.
Bachelor Program of Biotechnology, College of Agriculture and Natural Resources, National Chung Hsing University, Taichung 402, Taiwan.
Molecules. 2022 Feb 4;27(3):1066. doi: 10.3390/molecules27031066.
Acrylamide (ACR) is present in high-temperature-processed high-carbohydrate foods, cigarette smoke, and industrial pollution. Chronic exposure to ACR may induce neurotoxicity from reactive oxygen species (ROS); however, the mechanisms underlying ACR-induced neurotoxicity remain unclear. We studied 28-day subacute ACR toxicity by repeatedly feeding ACR (0, 15, or 30 mg/kg) to rats. We conducted RNA sequencing and Western blot analyses to identify differences in mRNA expression in the blood and in protein expression in the brain tissues, respectively, of the rats. AQP4 transient transfection was performed to identify potential associations with protein regulation. The rats treated with 30 mg/kg ACR exhibited hind-limb muscle weakness. Matrix metalloproteinase (MMP9) expression was higher in the ACR-treated group than in the control group. ACR induced MMP-9 and AQP4 protein expression in the brain tissues of the rats, which subsequently presented with neurotoxicity. In the in vitro study, Neuro-2a cells were transiently transfected with AQP4, which inhibited MMP-9 and TNF receptor-associated factor 6 (TRAF6) expression, and inhibited ACR induced expression of TRAF6, IκBα, and nuclear factor κB (NFκB). Using a combination of in vivo and in vitro experiments, this study revealed that depressive symptoms associated with ACR-induced neurotoxicity are associated with downregulation of AQP4 and induction of the TRAF6 pathway.
丙烯酰胺（ACR）存在于高温加工的高碳水化合物食品、香烟烟雾和工业污染中。慢性接触丙烯酰胺可能会导致活性氧（ROS）引起的神经毒性；然而，丙烯酰胺诱导的神经毒性的机制尚不清楚。我们通过反复给大鼠喂食丙烯酰胺（0、15 或 30mg/kg）来研究 28 天的亚急性丙烯酰胺毒性。我们进行了 RNA 测序和 Western blot 分析，分别鉴定了大鼠血液中 mRNA 表达的差异和脑组织中蛋白质表达的差异。进行了水通道蛋白 4（AQP4）瞬时转染，以鉴定与蛋白质调节的潜在关联。用 30mg/kg 丙烯酰胺处理的大鼠表现出后肢肌肉无力。与对照组相比，丙烯酰胺处理组的基质金属蛋白酶（MMP9）表达更高。丙烯酰胺诱导大鼠脑组织中 MMP-9 和 AQP4 蛋白表达，随后表现出神经毒性。在体外研究中，瞬时转染了 AQP4 的 Neuro-2a 细胞抑制了 MMP-9 和 TNF 受体相关因子 6（TRAF6）的表达，并抑制了 ACR 诱导的 TRAF6、IκBα 和核因子κB（NFκB）的表达。通过体内和体外实验的结合，本研究揭示了与丙烯酰胺诱导的神经毒性相关的抑郁症状与 AQP4 的下调和 TRAF6 途径的诱导有关。
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