Akter Salina, Uddin Kazi Rasel, Sasaki Hiroyuki, Shibata Shigenobu
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
Front Pharmacol. 2020 Mar 17;11:330. doi: 10.3389/fphar.2020.00330. eCollection 2020.
A high-fat diet (HFD) can induce obesity and metabolic disorders that are closely associated with cognitive impairments, and the progression of several psychiatric disorders such as anxiety. We have previously demonstrated the anxiolytic-like effect of Gamma oryzanol (GORZ) in chronic restraint stressed mice.
We studied the neurochemical and molecular mechanisms that underlie the preventive effect of GORZ in HFD-induced anxiety-like behaviors, monoaminergic dysfunction, and inflammation.
Eight-week-old Institute of Cancer (ICR) male mice weighing 33-34 g were divided into the following groups and free-fed for 8 weeks: control (14% casein, AIN 93M); HFD; HFD + GORZ (0.5% GORZ). Body weight gain was checked weekly. The anxiolytic-like effects of GORZ were examined open-field test (OFT) and elevated plus maze (EPM) test. Brain levels of monoamines [5-hydroxy tryptamine (5-HT), dopamine (DA), and norepinephrine (NE)] and their metabolites [5-hydroxyindole acetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG)], proinflammatory cytokines such as tumor necrosis factor-α () mRNA levels, and interleukin 1-β () mRNA levels in the cerebral cortex and amygdala were examined using high-performance liquid chromatography-electrochemical detection (HPLC-ECD), and real-time reverse transcription-polymerase chain reaction (RT-PCR), respectively.
Mice fed a HFD for eight weeks showed anxiety-like behaviors in association with HFD-induced body weight gain. GORZ potentially blocked HFD-induced anxiety-like behaviors significant improvement of the primary behavioral parameters in behavioral tests, with a minor reduction in HFD-induced body weight gain. Furthermore, GORZ treatment significantly downregulated HFD-induced upregulation of dopamine levels in the brain's amygdala. Significant reduction of the relative mRNA expression of and was also observed in the amygdala of HFD + GORZ mice, compared to HFD mice.
Our findings strongly suggest that 0.5% GORZ exerts anxiolytic-like effects, possibly through downregulation of dopamine, and expression of proinflammatory cytokines and in the case of chronic HFD exposure.
高脂饮食（HFD）可诱发肥胖和代谢紊乱，这些与认知障碍以及几种精神疾病如焦虑症的进展密切相关。我们之前已证明γ-谷维素（GORZ）对慢性束缚应激小鼠具有抗焦虑样作用。
我们研究了GORZ对高脂饮食诱导的焦虑样行为、单胺能功能障碍和炎症的预防作用所涉及的神经化学和分子机制。
将8周龄、体重33 - 34 g的雄性癌症研究所（ICR）小鼠分为以下几组，并自由进食8周：对照组（14%酪蛋白，AIN 93M）；高脂饮食组；高脂饮食 + GORZ组（0.5% GORZ）。每周检查体重增加情况。通过旷场试验（OFT）和高架十字迷宫（EPM）试验检测GORZ的抗焦虑样作用。分别使用高效液相色谱 - 电化学检测法（HPLC - ECD）和实时逆转录 - 聚合酶链反应（RT - PCR）检测大脑皮层和杏仁核中单胺类物质[5 - 羟色胺（5 - HT）、多巴胺（DA）和去甲肾上腺素（NE）]及其代谢产物[5 - 羟吲哚乙酸（5 - HIAA）、高香草酸（HVA）和3 - 甲氧基 - 4 - 羟基苯乙二醇（MHPG）]的脑内水平、促炎细胞因子如肿瘤坏死因子 - α（）mRNA水平以及白细胞介素1 - β（）mRNA水平。
高脂饮食喂养8周的小鼠出现焦虑样行为，并伴有高脂饮食诱导的体重增加。GORZ可能通过行为测试中主要行为参数的显著改善来阻断高脂饮食诱导的焦虑样行为，同时使高脂饮食诱导的体重增加略有减少。此外，GORZ治疗显著下调了高脂饮食诱导的大脑杏仁核中多巴胺水平的上调。与高脂饮食组小鼠相比，高脂饮食 + GORZ组小鼠杏仁核中 和 的相对mRNA表达也显著降低。
我们的研究结果强烈表明，0.5%的GORZ可能通过下调多巴胺以及在慢性高脂饮食暴露情况下促炎细胞因子 和 的表达发挥抗焦虑样作用。
