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3705564 
Journal Article 
Abstract 
Modeling complex environments in rats: Neurobehavioral phenotype of manganese overexposure, iron deficiency, and developmental stress interactions 
Amos-Kroohs, R; Davenport, L; Bloor, C; Vorhees, C; Williams, M 
2014 
1 
Neurotoxicology and Teratology
ISSN: 0892-0362
EISSN: 1872-9738 
43 
87 
English 
WOS:000338621800045 
Manganese (Mn) is neurotoxic at higher concentrations. Mn toxicity occurs in children from sources such as soy-based infant formulas, well-water, and air pollution near heavy manufacturing. Children's gastrointestinal systems allow Mn to more readily enter circulation and accumulate in the brain. Subclinical iron (Fe) deficiency (FeD), which affects up to 15% of US children, exacerbates Mn toxicity due to increased Mn bioavailability during FeD. FeD is prevalent in impoverished and low socioeconomic environments that are considered stressors. To model developmental stress (DS), pregnant rats and their litters were housed in cages with a wire grid floor or standard bedding from embryonic day (E)7 to postnatal day (P)28. Dams were fed a 90% Fe deficient or standard NIH-07 diet from E15 through P28. Within each litter, different offspring were treated with 100 mg/kg Mn (100Mn) by oral gavage or vehicle (VEH) from P4 to P28. Behavioral assays were run in offspring at post-weaning and adult time points. As adults, offspring were also tested in both spatial and non-spatial learning tasks. 100Mn animals show learning deficits in both the Morris (MWM) and Cincinnati water mazes (CWM). These animals also had decreased sociability at both ages, and altered locomotor activity that was age dependent. However, animals were not different from VEH controls in tests of anxiety and depression. The FeD*DS groups also showed deficits in several of these tests. Separately DS or FeD was found to significantly interact with 100Mn in a task dependent manner. For example, in acoustic startle response (ASR), 100Mn*DS animals showed exaggerated startle responses at younger ages. As adults, this group also showed increased errors in the CWM that were exaggerated compared to either group alone. FeD showed different effects. Together these data suggest that multifactorial models may reveal effects not observed when only one factor is studied at a time. (Supported by NIH T32 ES07051 and P30 ES006096.) 
38th Annual Meeting of the Neurobehavioral Teratology Society 
Bellevue, WA 
June 28 - July 2, 2014