Effect of acrylamide-induced neurotoxicity in a primary astrocytes/microglial co-culture model.
Acrylamide (AA), is a common food contaminant generated by heat processing. Astrocytes and microglia are the two major glial cell types in the brain that play pivotal but different roles in maintaining optimal brain function. The objective of this study is to investigate the neurotoxicity of AA, using a primary astrocytes/microglia co-culture model. Co-cultural cells obtained from Balb/c mice were cultured and treated with 0-1.0mM AA for 24-96h. Cell viability, reactive oxygen species (ROS) generation, oxidative end produces formation and glutathione (GSH) levels were measured. The expression of nuclear-E2-related factor 2(Nrf2), and nuclear factor kappa-beta (NF-κB) and selected down-stream genes were measured. Results showed that AA treatment led toa dose-dependent toxicity. Oxidative stress was induced as indicated by an increase of ROS, a decrease of GSH levels, and an increase in the formation of 4-hydroxynonenal-adduct and 8-hydroxy-2-deoxyguanosine-adduct. Both Nrf2 and NF-κB pathway contributed to the initiation of oxidative stress but the timing of two factors was different. Nrf2 and its related downstream genes were activated earlier than that in NF-κB pathway. In conclusion, AA-induced neurotoxicity attribute to oxidative stress via Nrf2 and NF-κB pathway. Moreover, the co-culture cell model was proven to be a viable model to study AA neurotoxicity.
College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China; Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
Mengyao
M
Zhao
Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
Fu Sheng Lewis
FSL
Wang
College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China.
Xiao Song
XS
Hu
College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China. Electronic address: chenfangch@sina.com.
Fang
F
Chen
Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada. Electronic address: laurie.chan@uottawa.ca.
Hing Man
HM
Chan
D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
D016207:Cytokines; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D020106:Acrylamide; D005978:Glutathione; D019803:Glutathione Disulfide
Acrylamide; Astrocytes; Co-cultural cells; Microglia; Neurotoxicity; Oxidative stress