Cognitive and behavioral deficits in a developmental model of multifactorial environmental exposure
Saturday, Nov 09, 2013, 4:00 PM - 5:00 PM
++C.07.k. Animal models and mechanisms
*R. M. AMOS-KROOHS
, L. L. DAVENPORT
, A. GUTIERREZ
, N. ATANSANOVA
, C. V. VORHEES
, M. T. WILLIAMS
Divison of Neurol., Cincinnati Children's Hosp. Med. Ctr., Cincinnati, OH;
Philosophy, Univ. of Cincinnati, Cincinnati, OH
Manganese (Mn), a trace dietary nutrient, is neurotoxic at higher concentrations. Mn toxicity occurs in children from sources such as soy-based infant formulas, well-water in some regions, and air pollution in areas with heavy manufacturing. Unlike adults, children’s gastrointestinal systems allow Mn to more readily enter circulation and accumulate in brain tissue. Subclinical iron (Fe) deficiency (FeD) exacerbates Mn toxicity due to bioavailability changes and lack of competitive inhibition. In the United States, all forms of FeD affect up to 15% of children under five years of age (CDC). FeD is more prevalent in impoverished and low socioeconomic circumstances and has been shown to be a developmental stressor. To model developmental stress (DS), half the pregnant rats and their litters were housed in cages with a wire grid floor in lieu of bedding and half in cages with standard bedding from embryonic day (E) 7 to postnatal day (P) 28. Animals were also fed a diet with 90% less Fe than the standard NIH-07 diet from E15 through P28 or a standard diet. Within each litter, different offspring were treated with 100 mg/kg Mn (100Mn) by oral gavage or vehicle from P4 to P28. Offspring were behaviorally phenotyped after weaning and as adults, beginning on P29 and P60, respectively. Anxiety-related behaviors and sucrose preference were decreased in 100Mn-treated animals, especially at P28. In the elevated zero maze on P28, 100Mn-treated animals had decreased initial latency to enter and increased entries into open quadrants. 100Mn-treated animals (whether FeD or DS) exhibited anhedonia in the sucrose preference test. In a social novelty task, younger DS-treated animals showed decreased interaction time with a stranger conspecific. As adults, 100Mn-treated animals exhibited a similar pattern. Locomotor activity, forced swim, and acoustic startle response (ASR) data are not yet analyzed. Adult animals were also tested in the Morris water maze (MWM) and Cincinnati water maze (CWM) tests of allocentric and egocentric learning and memory. MWM probe data showed decreased platform crossings in DS*FeD*100Mn groups during reversal and shifted phases but not during acquisition. In the CWM, DS*FeD groups had increased errors and latency to the goal. These data show that the interaction of these three treatments produce effects that are not predicted by only a single treatment.
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