Abstract
Acrylamide, a well-documented neurotoxicant, is commonly found as a byproduct of the Maillard reaction in carbohydrate-rich foods. Numerous studies have indicated that acrylamide-induced apoptosis accompanied by mitochondrial dysfunction contributes to its neurotoxicity. However, the mechanisms of how acrylamide causes mitochondrial impairment is not well understood. In this study, we observed destroyed redox balance, accumulated mitochondrial reactive oxygen species (ROS), damaged mitochondrial structures, and activated apoptosis in astrocytes following acrylamide treatment. Furthermore, acrylamide decreased the expression of mitochondrial biogenesis- and dynamics-related genes, including PGC-1α, TFAM, Mfn2, and Opa1, and altered the expression of mitochondrial DNA (mtDNA)-encoded mitochondrial respiratory chain complexes, along with the inhibited mitochondrial respiration. Pretreatment with a mitochondrial ROS scavenger mitoquinone dramatically restored the expressions of PGC-1α, TFAM, Mfn2, and Opa1; protected the mitochondrial structure; and decreased acrylamide-induced apoptosis. Further in vivo experiments confirmed that acrylamide decreased the expressions of PGC-1α, TFAM, Mfn2, and Opa1 in rat brain tissues. These results revealed that acrylamide triggered the mitochondrial ROS accumulation to interfere with mitochondrial biogenesis and dynamics, causing mtDNA damage and finally resulting in mitochondrial dysfunction and apoptosis.