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Chronic acrylamide exposure induced glia cell activation, NLRP3 infl-ammasome upregulation and cognitive impairment
- Source :
- Toxicology and Applied Pharmacology. 393:114949
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Acrylamide (ACR), a potential neurotoxin, is present in diet and drinking water. Dietary exposure contributes to cognitive impairment, but relevant mechanism information is limited. Neuroinflammation plays important roles in neurodegenerative disorders. This study aimed to explore whether chronic acrylamide exposure induced neuronal lesions, microglial activation, NLRP3 inflammasome-mediated neuroinflammation and cognitive impairment. For this purpose, 36 Sprague-Dawley (SD) rats were randomly divided into three groups (n = 12/group) and maintained on treated drinking water providing dosages of 0, 0.5, or 5 mg/kg/day ACR for 12 months. Chronic exposure to ACR caused gait abnormality and cognitive dysfunction, which was associated with neuronal lesions, decrease in synapse associated proteins including synapsin I (SYN1), synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), neurogenesis suppression as shown by reduced brain derived neurotrophic factor (BDNF) and doublecortin (DCX) in the hippocampus and frontal cortex. ACR stimulated glial proliferation and microglial activation by increasing GFAP+, Iba-1+, Iba-1+CD68+ positive cells. ACR markedly upregulated the protein levels of NLRP3 inflammasome constituents NLRP3, caspase-1 and increased pro-IL-1β and IL-1β. ACR elevated the protein P62 to suppress NLPR3 inflammasome cleavage. Inflammatory cytokines including TNF-α, IL-6 and Cox-2 were also significantly increased after NF-κB pathway activation, which aggravated neuronal lesions and caused memory deficits. This work helped to propose the possible mechanism of chronic exposure of ACR-induced neurotoxicity.
- Subjects :
- Male
0301 basic medicine
Synapsin I
medicine.medical_specialty
Doublecortin Protein
Inflammasomes
Toxicology
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Internal medicine
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Animals
Cognitive Dysfunction
Maze Learning
Gait Disorders, Neurologic
Neuroinflammation
Spatial Memory
Pharmacology
Brain-derived neurotrophic factor
Acrylamide
biology
business.industry
Neurotoxicity
Inflammasome
Macrophage Activation
medicine.disease
Rats
Up-Regulation
Doublecortin
Oxidative Stress
030104 developmental biology
Endocrinology
nervous system
030220 oncology & carcinogenesis
Synaptophysin
biology.protein
Cytokines
Inflammation Mediators
business
Cell activation
Neuroglia
medicine.drug
Subjects
Details
- ISSN :
- 0041008X
- Volume :
- 393
- Database :
- OpenAIRE
- Journal :
- Toxicology and Applied Pharmacology
- Accession number :
- edsair.doi.dedup.....e495aab1b7d3a0683d6abbb86367f790