Archives of Toxicology

, Volume 93, Issue 2, pp 467–486 | Cite as

Acrylamide aggravates cognitive deficits at night period via the gut–brain axis by reprogramming the brain circadian clock

  • Xintong Tan
  • Jin Ye
  • Weiqi Liu
  • Beita Zhao
  • Xu Shi
  • Chengliang Zhang
  • Zhigang Liu
  • Xuebo LiuEmail author
Organ Toxicity and Mechanisms


Imbalance of the circadian rhythm leads to pathologies including obesity, neurodegenerative diseases, and even cancer. Acrylamide (ACR) is a chronic neurotoxin which can lead to carcinogenicity, reproduction toxicity, teratogenicity, and neurotoxicity. The aim of this study was to reveal a potential mechanism of ACR-triggered neurotoxicity related to circadian clock in mice brain. For this purpose, 80 3-month-old C57/BL6J mice were randomly divided into two groups (n = 40/group): the control group was fed a standard diet (AIN-93M) with pure water, and the ACR group was fed a standard diet (AIN-93M) with 0.003% ACR in drinking water for 16 weeks. In the current study, ACR treatment induced circadian disorder and suppressed the circadian-related protein expressions in mice brain. Furthermore, ACR diet aggravated the cognitive dysfunction and spatial memory loss at night phase. Consistent with these results, ACR caused cognitive defects in the night period by down-regulating the ERK/cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathways and the expression of synaptosomal-related protein SNAP-25 and PSD-95. Moreover, excessive autophagy phenomenon also occurred in mice hippocampus in the night phase under ACR administration. Of note, ACR stimulated the brain inflammatory reaction via affecting the intestinal barrier integrity and increasing the levels of circulating LPS, IL-1β and TNF-α. Above all, the present research discovered that ACR is a potential circadian-depressing compound that influences cognitive function in mice brain.


Acrylamide Circadian rhythm Cognitive impairment Synaptic plasticity Gut–brain axis 



This work was supported by grants from the National Key Research and Development Program of China (No. 2016YFD0400601), the National Natural Science Foundation of China (No. 31271810), Young Talent Fund of University Association for Science and Technology in Shaanxi, China (20170201), China Postdoctoral Science Foundation (2018T111104) and the Fundamental research funds for the central universities (2452017141) supported this research.

Compliance with ethical standards

Ethics statement

All of the animal experimental procedures followed the Guide for the Care and Use of Laboratory Animals: Eighth Edition, ISBN-10: 0-309-15396-4, and the animal protocol was approved by the animal ethics committee of Xi’an Jiaotong University. All surgeries were performed under anesthesia and all efforts were made to minimize suffering.

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

204_2018_2340_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 16 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Xintong Tan
    • 1
  • Jin Ye
    • 1
  • Weiqi Liu
    • 1
  • Beita Zhao
    • 1
  • Xu Shi
    • 1
  • Chengliang Zhang
    • 1
  • Zhigang Liu
    • 1
  • Xuebo Liu
    • 1
    Email author
  1. 1.Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and EngineeringNorthwest A&F UniversityYanglingChina

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