title: Low circulating levels of bisphenol-A induce cognitive deficits and loss of asymmetric spine synapses in dorsolateral prefrontal cortex and hippocampus of adult male monkeys.
abstract: Bisphenol-A (BPA) is widely used in the manufacture of plastics, epoxy resins, and certain paper products. A majority of the population in the developed world is routinely exposed to BPA from multiple sources and has significant circulating levels of BPA. Although BPA is categorized as an endocrine disruptor with a growing literature on adverse effects, it is uncertain whether cognitive dysfunction is induced in humans by exposure to BPA. The present study examined the impact of BPA in primate brain by exposing adult male vervet monkeys for 4 weeks continuously to circulating levels of BPA that were in the range measured in studies of humans environmentally exposed to BPA. This regimen of exposure to BPA decreased both working memory accuracy and the number of excitatory synaptic inputs on dendritic spines of pyramidal neurons in two brain regions that are necessary for working memory (prefrontal cortex and hippocampus). These observed behavioral and synaptic effects were ameliorated following withdrawal from BPA. As Old World monkeys (e.g., vervets) and humans share some uniquely primate morphological, endocrine, and cognitive traits, this study indicates the potential for significant cognitive disruption following exposure of humans to BPA.
authors.affiliation: Department of Psychiatry, Yale University, School of Medicine, New Haven, Connecticut.
authors.forename: John D
authors.initials: JD
authors.lastname: Elsworth
authors.forename: James D
authors.initials: JD
authors.lastname: Jentsch
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Groman
authors.forename: Robert H
authors.initials: RH
authors.lastname: Roth
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Redmond
authors.forename: Csaba
authors.initials: C
authors.lastname: Leranth
mesh_terms: D000395:Air Pollutants, Occupational / Q000097:blood / Q000633:toxicity*; D000818:Animals; D001559:Benzhydryl Compounds / Q000097:blood / Q000633:toxicity*; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D003072:Cognition Disorders / Q000139:chemically induced* / Q000473:pathology; D049229:Dendritic Spines / Q000187:drug effects / Q000648:ultrastructure; D004781:Environmental Exposure; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008854:Microscopy, Electron; D023421:Models, Animal; D009483:Neuropsychological Tests; D010636:Phenols / Q000097:blood / Q000633:toxicity*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000648:ultrastructure; D017966:Pyramidal Cells / Q000187:drug effects / Q000648:ultrastructure; D013569:Synapses / Q000187:drug effects* / Q000648:ultrastructure; D000098826:Bisphenol A Compounds
chemical_list: D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: dopamine; endocrine disruptor; working memory