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

Izumi, Yukitoshi; Fujii, Chika; O’Dell, Kazuko A.; Zorumski, Charles F.

doi:10.1038/s41598-022-16762-7

Cited by 13 publications

(21 citation statements)

References 50 publications

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“…However, how acrylamide exposure is linked to anxiety and depression still remains obscure. To further understand in-depth neurological damage, evidence supported that chronic exposure to acrylamide results in the accumulation of misfolded proteins, neuroinflammation, and neuronal apoptosis, leading to progressive neurodegeneration ( 21 , 22 ). Moreover, a 2-wk exposure to acrylamide induces acute inflammatory death with hyperlipidemia using human macrophages, dermal cells, and zebrafish models ( 23 ).…”

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confidence: 99%

High fried food consumption impacts anxiety and depression due to lipid metabolism disturbance and neuroinflammation

Wang

Wan

Zhuang

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Western dietary patterns have been unfavorably linked with mental health. However, the long-term effects of habitual fried food consumption on anxiety and depression and underlying mechanisms remain unclear. Our population-based study with 140,728 people revealed that frequent fried food consumption, especially fried potato consumption, is strongly associated with 12% and 7% higher risk of anxiety and depression, respectively. The associations were more pronounced among male and younger consumers. Consistently, long-term exposure to acrylamide, a representative food processing contaminant in fried products, exacerbates scototaxis and thigmotaxis, and further impairs exploration ability and sociality of adult zebrafish, showing anxiety- and depressive-like behaviors. Moreover, treatment with acrylamide significantly down-regulates the gene expression of tjp2a related to the permeability of blood–brain barrier. Multiomics analysis showed that chronic exposure to acrylamide induces cerebral lipid metabolism disturbance and neuroinflammation. PPAR signaling pathway mediates acrylamide-induced lipid metabolism disorder in the brain of zebrafish. Especially, chronic exposure to acrylamide dysregulates sphingolipid and phospholipid metabolism, which plays important roles in the development of anxiety and depression symptoms. In addition, acrylamide promotes lipid peroxidation and oxidation stress, which participate in cerebral neuroinflammation. Acrylamide dramatically increases the markers of lipid peroxidation, including (±)5-HETE, 11(S)-HETE, 5-oxoETE, and up-regulates the expression of proinflammatory lipid mediators such as (±)12-HETE and 14(S)-HDHA, indicating elevated cerebral inflammatory status after chronic exposure to acrylamide. Together, these results both epidemiologically and mechanistically provide strong evidence to unravel the mechanism of acrylamide-triggered anxiety and depression, and highlight the significance of reducing fried food consumption for mental health.

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mentioning

confidence: 99%

High fried food consumption impacts anxiety and depression due to lipid metabolism disturbance and neuroinflammation

Wang

Wan

Zhuang

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“…The potential mechanisms through which ACR causes learning and memory impairment include neuronal damage, inflammatory response, neurotransmitter imbalance, oxidative stress, and release of neuroinflammatory factors, etc (Izumi et al, 2022;Lee et al, 2018;Liu et al, 2020;Quan et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide

Wang,

Zhang,

Pan

et al. 2024

Preprint

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The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear. We used proteomics technology to analyze the serum of the ACR occupationally exposed population and screen out target proteins related to learning and memory. Through in vivo, in vitro experiments, and transgenic mouse models, we investigated the selected target protein to elucidate. Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomic. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P < 0.05). Subsequent in vitro experiments using eEF2K siRNA and in vivo experiments with eEF2K-knockout mice demonstrated significant improvements in abnormal indicators related to ACR-induced learning and memory deficits (P < 0.05). Proteomic analysis of the hippocampus revealed Lpcat1 as a crucial downstream protein regulated by eEF2K. KEGG analysis indicated that eEF2K may play a role in the process of ACR-induced learning and memory impairment by affecting ether lipid metabolism. In summary, eEF2K as a pivotal target in the mechanisms underlying ACR-induced learning and memory impairment, providing robust evidence for potential clinical interventions targeting.

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“…Hippocampal slices were prepared from postnatal day (P) 28–32 male albino rats using previously described methods 21 , 22 . Dissected hippocampi were pinned on an agar base in ice-cold artificial cerebrospinal fluid (ACSF) containing (in mM): 124 NaCl, 5 KCl, 2 MgSO 4 , 2 CaCl 2 , 1.25 NaH 2 PO 4 , 22 NaHCO 3 , 10 glucose, bubbled with 95% O 2 –5% CO 2 at 4–6 °C.…”

Section: Methodsmentioning

confidence: 99%

The herbicide glyphosate inhibits hippocampal long-term potentiation and learning through activation of pro-inflammatory signaling

Izumi,

O’Dell,

Zorumski

2023

Sci Rep

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Glyphosate, a herbicide marketed as Roundup, is widely used but there are concerns this exposure could impair cognitive function. In the CA1 region of rat hippocampal slices, we investigated whether glyphosate alters synaptic transmission and long-term potentiation (LTP), a cellular model of learning and memory. Our hypothesis is that glyphosate alters neuronal function and impairs LTP induction via activation of pro-inflammatory processes. Roundup depressed excitatory synaptic potentials(EPSPs) in a dose-dependent manner with complete suppression at 2000 mg/L. At concentrations ≤ 20 mg/L Roundup did not affect basal transmission, but 4 mg/L Roundup administered for 30 min inhibited LTP induction. Acute administration of 10–100 μM glyphosate also inhibited LTP induction. Minocycline, an inhibitor of microglial activation, and TAK-242, an inhibitor of toll-like receptor 4 (TLR4), both overcame the inhibitory effects of 100 µM glyphosate. Similarly, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), a different TLR4 antagonist, overcame the inhibitory effects. In addition, ISRIB (integrated stress response inhibitor) and quercetin, an inhibitor of endoplasmic reticulum stress, overcame the inhibitory effects. We also observed that in vivo glyphosate injection (16.9 mg/kg i.p.) impaired one-trial inhibitory avoidance learning. This learning deficit was overcome by TAK-242. These observations indicate that glyphosate can impair cognitive function through pro-inflammatory signaling in microglia.

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

Cited by 13 publications

References 50 publications

High fried food consumption impacts anxiety and depression due to lipid metabolism disturbance and neuroinflammation

High fried food consumption impacts anxiety and depression due to lipid metabolism disturbance and neuroinflammation

Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide

The herbicide glyphosate inhibits hippocampal long-term potentiation and learning through activation of pro-inflammatory signaling

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