title: Bisphenol A disrupts glucose transport and neurophysiological role of IR/IRS/AKT/GSK3β axis in the brain of male mice.
abstract: Bisphenol A (BPA), one of the most prevalent chemicals for daily use, was recently reported to disturb the homeostasis of energy metabolism and insulin signaling pathways, which might contribute to the increasing prevalence rate of mild cognitive impairment (MCI). However, the underlying mechanisms are remained poorly understood. Here we studied the effects of low dose BPA on glucose transport and the IR/IRS/AKT/GSK3β axis in adult male mice to delineate the association between insulin signaling disruption and neurotoxicity mediated by BPA. Mice were treated with subcutaneous injection of 100μg/kg/d BPA or vehicle for 30 days, then the insulin signaling and glucose transporters in the hippocampus and prefrontal cortex were detected by western blot. Our results showed that mice treated with BPA displayed significant decrease of insulin sensitivity, and in glucose transporter 1, 3 (GLUT1, 3) protein levels in mouse brain. Meanwhile, hyperactivation of IR/IRS/AKT/GSK3β axis was detected in the brain of BPA treated mice. Noteworthily, significant increases of phosphorylated tau and β-APP were observed in BPA treated mice. These results strongly suggest that BPA exposure significantly disrupts brain insulin signaling and might be considered as a potential risk factor for neurodegenerative diseases.
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Donglong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210000, China.
authors.forename: Jingli
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: wangjun@njmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: hxiao@njmu.edu.cn.
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D052244:Endocrine Disruptors / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D051379:Mice; D010636:Phenols / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D005947:Glucose; D051246:Glucose Transport Proteins, Facilitative; D000071679:Glycogen Synthase Kinase 3 beta; D010636:Phenols; D051057:Proto-Oncogene Proteins c-akt; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: BPA; Glucose transporters; Insulin signaling; Mice; Neurodegenerative diseases