title: Perinatal exposure to Di-(2-ethylhexyl)-Phthalate leads to cognitive dysfunction and phospho-tau level increase in aged rats.
abstract: Di-(2-ethylhexyl)-Phthalate (DEHP) can affect glucose and insulin homeostasis in periphery and lead to insulin resistance, especially exposure of DEHP during critical developmental period. Given the potential relationship between insulin resistance and pathogenesis of Alzheimer's disease (AD) in elderly life, we investigated the relationship between perinatal DEHP exposure and AD pathogenesis. Our results suggested that perinatal exposure to DEHP can affect the expression of insulin and insulin-Akt- GSK-3β signal pathway in hippocampus. Furthermore, impaired cognitive ability and increased level of phospho-Tau was observed in DEHP-exposed rat offspring (1.25 ± 0.11 vs. 0.47 ± 0.07, P < 0.05). The present study demonstrates that perinatal exposure to DEHP may be a potential risk factor for AD pathogenesis associated with insulin resistance and insulin metabolism disorder in the hippocampus.
authors.affiliation: Department of General Thoracic Surgery, Tongji Hospital Attached to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Jin-Bao
authors.initials: JB
authors.lastname: Ban
authors.forename: Ni
authors.initials: N
authors.lastname: Zhang
authors.forename: Yu-Kun
authors.initials: YK
authors.lastname: Zu
authors.forename: Wen-Xiao
authors.initials: WX
authors.lastname: Sun
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced*; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D007328:Insulin; C489131:Mapt protein, rat; D016875:tau Proteins; D004051:Diethylhexyl Phthalate; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3