3,3'-Diindolylmethane and 1,4-dihydroxy-2-naphthoic acid prevent chronic mild stress induced depressive-like behaviors in female mice.
3,3'-Diindolylmethane and 1,4-dihydroxy-2-naphthoic acid prevent chronic mild stress induced depressive-like behaviors in female mice.
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3,3'-二迪丁烷基甲烷和1,4-二羟基-2-萘酸可预防慢性轻度应激诱导雌性小鼠的抑郁样行为。
DOI：
10.1016/j.jad.2022.04.106
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发表时间：
2022-07-15
影响因子：
6.6
通讯作者：
Eitan, Shoshana
中科院分区：
文献类型：
--
作者：
Madison, Caitlin A.;Kuempel, Jacob;Albrecht, Georgia Lee;Hillbrick, Lauren;Jayaraman, Arul;Safe, Stephen;Chapkin, Robert S.;Eitan, Shoshana
关键词：
目前治疗抑郁症的药物治疗有时无效，可能会产生有害的副作用，干扰患者的依从性。这项研究考察了饮食和微生物来源的芳烃受体(AhR)配体3，3‘-二吲哚甲烷(DIM)和1，4-二羟基-2-萘甲酸(1，4-DHNA)的潜在抗抑郁作用。雌性C57BL/6小鼠接受不可预测的慢性轻度应激(UCMS)或非应激。UCMS前三周，每天给小鼠灌胃赋形剂或20 mg/kg的DIM，1，4-DHNA或AhR失活异构体3，7-DHNA；另一组在开始给药前给予UCMS两周。通过蔗糖偏好试验检测小鼠的快感缺乏样行为。此外，在UCMS和配基注射开始之前和结束时，在开阔场地、光照/黑暗、高架加迷宫、新奇诱导的吞噬减少和大理石埋藏试验中，检测了小鼠的焦虑水平。在实验结束时，他们还在Morris水迷宫(MWM)任务中进行了检查。DIM和1，4-DHNA，但不是3，7-DHNA，都成功地预防和逆转了UCMS诱导的快感缺乏样行为。此外，DIM和DHNA对焦虑水平几乎没有影响，也不会导致空间学习障碍。需要进一步的研究来确定DIM和1，4-DHNA的抗抑郁作用在多大程度上可以归因于它们作为AhR配体的活性。我们的发现表明，饮食和微生物来源的AhR配体可能作为潜在的抗抑郁药物在临床上应用。未来的研究有必要阐明AhR在抑郁症样状态中的作用和潜在的作用机制。
Current pharmaceutical treatments for depression are sometimes ineffective and may have unwanted side effects that interfere with patient compliance. This study examined the potential antidepressant-like effects of dietary- and microbial-derived aryl hydrocarbon receptor (AhR) ligands, 3,3′-diindolylmethane (DIM) and 1,4-dihydroxy-2-naphthoic acid (1,4-DHNA). Female C57BL/6 mice were subjected to unpredictable chronic mild stress (UCMS) or were unstressed. For three weeks prior to UCMS mice were fed daily with vehicle or 20 mg/kg DIM, 1,4-DHNA or AhR-inactive isomer 3,7-DHNA; another group was subjected to two weeks UCMS before ligand administration began. Mice were examined for anhedonia-like behavior as measured by the sucrose preference test. Additionally, anxiety levels of the mice were examined before UCMS and ligand administration began and at the end in the open field, light/dark, elevated plus maze, novelty-induced hypophagia, and marble burying tests. At the end of the experiment they were also examined in the Morris water maze (MWM) task. Both DIM and 1,4-DHNA, but not 3,7-DHNA, successfully prevented and reversed UCMS-induced anhedonia-like behavior. Furthermore, both DIM and DHNA had little to no effect on anxiety levels and did not induce spatial learning deficits. Additional studies are required to determine to what degree the antidepressant-like effects of DIM and 1,4-DHNA can be attributed to their activities as AhR ligands. Our findings indicate that dietary and microbial-derived AhR ligands may have clinical applications as potential antidepressants. Future studies are necessary to elucidate the role of AhR in depression-like states and the underlying mechanisms of action.
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影响因子：
4.3
作者：
Yang, Sujuan;Tan, Lixi;Peng, Zhongxing
通讯作者：
Peng, Zhongxing
影响因子：
5
作者：
Willner P
通讯作者：
Willner P
肠道微生物群的改变通过宿主代谢介导的途径诱发抑郁样行为
影响因子：
11
作者：
Zheng, P.;Zeng, B.;Xie, P.
通讯作者：
Xie, P.
影响因子：
5.6
作者：
Xue, Ling;Pestka, James J.;Bjeldanes, Leonard F.
通讯作者：
Bjeldanes, Leonard F.