Effect of Dietary Exposure to Acrylamide on Diabetes-Associated Cognitive Dysfunction from the Perspectives of Oxidative Damage, Neuroinflammation, and Metabolic Disorders

Acrylamide is a toxic compound that is produced widely during food processing, but whether the daily dietaryconsumption of acrylamide can impair the cognitive dysfunction in diabetic individuals and the potential underlying mechanisms areunknown. The aim of the present study was to observe the changes in cognitive and memory performance caused by chronicacrylamide exposure and to evaluate its influence on the brain morphology, oxidative damage, neuroinflammation, and brainmetabolic disturbance. Goto-Kakizaki (GK) rats, a rat model of diabetes, were orally administered acrylamide at 1 mg/kg bodyweight for 8 weeks. The results of the novel object recognition and Y-maze tests showed that the consumption of acrylamidesignificantly aggravated diabetes-associated cognitive dysfunction in GK rats. Acrylamide increased reactive oxygen species andmalondialdehyde formation and reduced glutathione levels, catalase, and total antioxidant capacity activity, which caused asuccession of events associated with oxidative damage, including glial cell activation. After the activation of astrocytes and microglia,related cytokines, including interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and lipopolysaccharide, were released, amyloid beta-protein was accumulated, brain-derived neurotrophic factor was decreased, and the expression of caspase-3 and caspase-9 wasincreased, which aggravated neuroinflammation. Furthermore, there was perturbation of some important metabolites, includingglutamic acid, citric acid, pyruvic acid, lactate, and sphinganine, and their related glucose, amino acid, and energy metabolismpathways in the brain. This work helps to demonstrate the effect of consumption of acrylamide in the daily diet on diabetes-associated cognitive dysfunction and its underlying mechanisms.

Automated summary

This study examines the effects of chronic acrylamide exposure on cognitive and memory performance as well as its influence on brain morphology, oxidative damage, neuroinflammation, and brain metabolic disturbance in diabetes-induced rats.