title: Developmental manganese neurotoxicity in rats: Cognitive deficits in allocentric and egocentric learning and memory.
abstract: Manganese (Mn) is an essential element but neurotoxic at higher exposure levels. The effects of Mn overexposure (MnOE) on hippocampal and striatal-dependent learning and memory in rats were tested in combination with iron deficiency (FeD) and developmental stress that often co-occur with MnOE. Moderate FeD affects up to 15% of U.S. children and developmental stress is common in lower socio-economic areas where MnOE occurs. Pregnant Sprague-Dawley rats and their litters were housed in cages with or without (barren cage (BAR)) standard bedding from embryonic day (E)7 to postnatal day (P)28. Dams were fed a 90% FeD or iron sufficient (FeS) diet from E15-P28. Within each litter, separate offspring were treated with 100mg/kg Mn (MnOE) or vehicle (VEH) by gavage on alternate days from P4-28. Offspring were tested as adults in the Morris and Cincinnati water mazes. FeD and developmental stress interactively impaired spatial learning in the Morris water maze. Developmental stress and MnOE impaired learning and memory in both mazes. MnOE resulted in reduced CA1 hippocampal long-term potentiation (LTP) and increased levels of α-synuclein. Preweaning MnOE resulted in cognitive deficits on multiple domains of learning and memory accompanied by impaired LTP and α-synuclein changes, effects worsened by developmental stress.
authors.affiliation: Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States.
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Amos-Kroohs
authors.affiliation: Department of Environmental Health, University of Cincinnati, 3223 Eden Ave., Cincinnati, OH 45220, United States.
authors.forename: Laurie L
authors.initials: LL
authors.lastname: Davenport
authors.affiliation: Department of Philosophy and Religious Studies, University of Toledo, Toledo, OH 43606, United States.
authors.forename: Nina
authors.initials: N
authors.lastname: Atanasova
authors.affiliation: Graduate Program in Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 43267, United States.
authors.forename: Zuhair I
authors.initials: ZI
authors.lastname: Abdulla
authors.affiliation: Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Skelton
authors.affiliation: Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States.
authors.forename: Charles V
authors.initials: CV
authors.lastname: Vorhees
authors.affiliation: Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States. Electronic address: michael.williams@cchmc.org.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Williams
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D000090463:Iron Deficiencies; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D008345:Manganese / Q000633:toxicity*; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D013315:Stress, Psychological / Q000523:psychology*; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein; D008345:Manganese
keywords: Alpha-synuclein; Egocentric learning; Long-term potentiation; Manganese; Neurotoxicity; Spatial learning