Chronic acrylamide exposure induced glia cell activation, NLRP3 infl-ammasome upregulation and cognitive impairment

Liu, Ying; Zeng, Xing; Yan, Dandan; Wang, Yiqi; Wang, Na; Liu, Yufan; Tan, Aijun; Chen, Xiaoyi; Hong, Yan

doi:10.1016/j.taap.2020.114949

Cited by 35 publications

(21 citation statements)

References 59 publications

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“…Finally, food consumed as such, or after cooking processes, as well as water, may also contain internal or accidental components with a stimulating effect on NLRP3 inflammasome. Among these, mycotoxins (zearalenone, patulin, deoxynivalenol), trace metals (arsenic, cadmium), environmental and food contaminants (acrolein, 3-monochloropropane-1,2-diol, glycidol, and its esters), and acrylamide are few examples of NLRP3 activators, endowed with harmful inflammatory effects [ 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 ].…”

Section: Food and Nutraceuticals Components Bioavailability And Toxicitymentioning

confidence: 99%

Modulatory Properties of Food and Nutraceutical Components Targeting NLRP3 Inflammasome Activation

et al. 2022

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Inflammasomes are key intracellular multimeric proteins able to initiate the cellular inflammatory signaling pathway. NLRP3 inflammasome represents one of the main protein complexes involved in the development of inflammatory events, and its activity has been largely demonstrated to be connected with inflammatory or autoinflammatory disorders, including diabetes, gouty arthritis, liver fibrosis, Alzheimer’s disease, respiratory syndromes, atherosclerosis, and cancer initiation. In recent years, it has been demonstrated how dietary intake and nutritional status represent important environmental elements that can modulate metabolic inflammation, since food matrices are an important source of several bioactive compounds. In this review, an updated status of knowledge regarding food bioactive compounds as NLRP3 inflammasome modulators is discussed. Several chemical classes, namely polyphenols, organosulfurs, terpenes, fatty acids, proteins, amino acids, saponins, sterols, polysaccharides, carotenoids, vitamins, and probiotics, have been shown to possess NLRP3 inflammasome-modulating activity through in vitro and in vivo assays, mainly demonstrating an anti-NLRP3 inflammasome activity. Plant foods are particularly rich in important bioactive compounds, each of them can have different effects on the pathway of inflammatory response, confirming the importance of the nutritional pattern (food model) as a whole rather than any single nutrient or functional compound.

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Section: Food and Nutraceuticals Components Bioavailability And Toxicitymentioning

confidence: 99%

Modulatory Properties of Food and Nutraceutical Components Targeting NLRP3 Inflammasome Activation

et al. 2022

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“…Based on prior studies indicating that ACR can evoke inflammatory responses 11 , 13 , we examined the role of pro-inflammatory pathways in the effects of ACR. To test the involvement of pro-inflammatory signaling, we used TAK-242, a specific inhibitor of toll-like receptor 4 (TLR4), and LPSRS, an agent that also inhibits TLR4 in addition to non-canonical inflammasome activation 23 .…”

Section: Resultsmentioning

confidence: 99%

“…In Kupffer cells, 0.5–1 mM ACR induces ROS production in 24 h and increases expression of NLRP3 and IL-1β mRNA, which results in NLRP3 inflammasome formation 36 . In rats, chronic (12 month) exposure to ACR (5 mg/kg/day) markedly upregulates protein levels of NLRP3 inflammasome constituents including NLRP3 caspase-1, and pro-IL-1β and IL-1β in hippocampus and frontal cortex 11 .…”

Section: Discussionmentioning

confidence: 99%

“…Cognitive decline is also suggested in elderly people who ingest greater amounts of ACR over a number of years 9 , suggesting that dietary exposure may cause CNS problems. Indeed, 16 week exposure to ACR in drinking water worsens cognitive deficits in mice 10 and more chronic exposure (12 months) in rats results in neuronal deficits in the hippocampus and cortex accompanied with poor performance in spatial memory tests 11 .…”

Section: Introductionmentioning

confidence: 99%

“…More recently, the possible involvement of inflammatory reactions in ACR toxicity is postulated. In animal models, increased levels of circulating lipopolysaccharide (LPS), interleukin-1ß (IL-1β) and tumor necrosis factor-ɑ (TNF-α) after dietary exposure 10 or robust upregulation of protein levels of nucleotide-binding oligomerization domain-3 (NLRP3) inflammasome constituents including NLRP3, caspase-1 and IL-1β after dietary exposure 11 were observed. Furthermore, Sui et al found that 24 h administration of 2.5 mM ACR increases levels of NLRP3 inflammasome constituents in BV2 microglia, suggesting that effects of ACR on NLRP3 can be acute 13 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Acrylamide inhibits long-term potentiation and learning involving microglia and pro-inflammatory signaling

Izumi

Fujii

O’Dell

et al. 2022

Sci Rep

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Acrylamide is a chemical used in various industries and a product following high-temperature cooking of vegetables containing asparagine. Environmental or dietary exposure to acrylamide could impair cognitive function because of its neurotoxicity. Using rat hippocampal slices, we tested whether acrylamide alters induction of long-term potentiation (LTP), a cellular model of learning and memory. We hypothesized that acrylamide impairs cognitive function via activation of pro-inflammatory cytokines because robust upregulation of NLRP3 inflammasome has been reported. Although acrylamide up to 3 mM did not alter basal synaptic transmission, incubation with 10 μM or acute administration of 100 μM acrylamide inhibited induction of LTP. Inhibitors of toll-like receptor 4 (TLR4), and minocycline, an inhibitor of microglial activation, overcame the effects of acrylamide on LTP induction. Furthermore, we observed that acrylamide failed to inhibit LTP after administration of MCC950, an inhibitor of NLRP3, or in the presence of Interleukin-1 receptor antagonist (IL-1Ra). We also found that in vivo acrylamide injection transiently impaired body weight gain and impaired one-trial inhibitory avoidance learning. This learning deficit was overcome by MCC950. These results indicate that cognitive impairment by acrylamide is mediated by mechanisms involving microglia and release of cytokines via NLRP3 activation.

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Acrylamide‐induced autophagy‐lysosomal pathway dysfunction contributing to neurotoxicity through targeting transcription factor EB

Yang

Zhang

et al. 2023

Food Frontiers

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Autophagy‐lysosomal pathway (ALP), a lysosome‐mediated self‐renewal process, is crucial for cell survival and death. Acrylamide (AA) is a neurotoxic compound produced during food thermal processing, and the mechanism underlying AA‐induced neurotoxicity remains elusive. In this study, we explored whether dysregulated ALP was involved in AA‐induced neurotoxicity and the underlying mechanism. We first evaluated the toxic effects of AA on the activation of apoptosis and NLRP3 pathway in human glioma U251 cells. We found that AA‐induced autophagy activation with the accumulation of an autophagy substrate P62, which implies the occurrence of autophagy‐lysosomal disorders. By using autophagy agonist PP242 and siRNA interfering ATG5, we demonstrated that ALP dysregulation contributed to AA‐induced apoptosis and NLRP3 inflammasome pathway activation. In addition, AA triggered ALP dysfunction by decreasing the expression of transcription factor EB (TFEB), and TFEB overexpression restored the lysosomal‐associated proteins and protected against AA‐induced apoptosis and inflammasome activation. Moreover, the autophagy agonist rapamycin restored AA‐induced ALP dysfunction by upregulating TFEB and prevented neurotoxicity. Overall, our study provides novel insights into the role of disrupted ALP in AA‐induced neurotoxicity and highlights that TFEB can be developed as a promising intervention target against AA‐induced neurotoxicity.

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Chronic acrylamide exposure induced glia cell activation, NLRP3 infl-ammasome upregulation and cognitive impairment

Cited by 35 publications

References 59 publications

Modulatory Properties of Food and Nutraceutical Components Targeting NLRP3 Inflammasome Activation

Modulatory Properties of Food and Nutraceutical Components Targeting NLRP3 Inflammasome Activation

Acrylamide inhibits long-term potentiation and learning involving microglia and pro-inflammatory signaling

Acrylamide‐induced autophagy‐lysosomal pathway dysfunction contributing to neurotoxicity through targeting transcription factor EB

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