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

Abstract

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.