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

Oct 31, 2018Archives of toxicology

Acrylamide worsens nighttime thinking problems by changing the gut-brain communication and brain’s internal clock

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Abstract

ACR treatment in mice led to cognitive dysfunction and circadian disorder over 16 weeks.

ACR induced a disruption of the circadian rhythm in the mice's brains.
Cognitive dysfunction and spatial memory loss were more pronounced during the night phase.
ACR treatment down-regulated key signaling pathways involved in cognitive function.
An increase in excessive autophagy was observed in the hippocampus of ACR-treated mice during the night.
ACR treatment triggered brain inflammation by compromising intestinal barrier integrity and elevating inflammatory markers.

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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.

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

Abstract

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