title: Effects of developmental manganese, stress, and the combination of both on monoamines, growth, and corticosterone.
abstract: Developmental exposure to manganese (Mn) or stress can each be detrimental to brain development. Here, Sprague-Dawley rats were exposed to two housing conditions and Mn from postnatal day (P)4-28. Within each litter two males and 2 females were assigned to the following groups: 0 (vehicle), 50, or 100 mg/kg Mn by oral gavage every other day. Half the litters were reared in cages with standard bedding and half with no bedding. One pair/group in each litter had an acute shallow water stressor before tissue collection (i.e., standing in shallow water). Separate litters were assessed at P11, 19, or 29. Mn-treated rats raised in standard cages showed no change in baseline corticosterone but following acute stress increased more than controls on P19; no Mn effects were seen on P11 or P29. Mn increased neostriatal dopamine in females at P19 and norepinephrine at P11 and P29. Mn increased hippocampal dopamine at P11 and P29 and 5-HT at P29 regardless of housing or sex. Mn had no effect on hypothalamic dopamine, but increased norepinephrine in males at P29 and 5-HT in males at all ages irrespective of rearing condition. Barren reared rats showed no or opposite effects of Mn, i.e., barren rearing + Mn attenuated corticosterone increases to acute stress. Barren rearing also altered the Mn-induced changes in dopamine and norepinephrine in the neostriatum, but not in the hippocampus. Barren rearing caused a Mn-associated increase in hypothalamic dopamine at P19 and P29 not seen in standard reared Mn-treated groups. Developmental Mn alters monoamines and corticosterone as a function of age, stress (acute and chronic), and sex.
authors.affiliation: Department of Pediatrics, Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Charles V
authors.initials: CV
authors.lastname: Vorhees
authors.affiliation: Department of Pediatrics, Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Devon L
authors.initials: DL
authors.lastname: Graham
authors.affiliation: Department of Pediatrics, Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Amos-Kroohs
authors.affiliation: Department of Pediatrics, Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Braun
authors.affiliation: Department of Pediatrics, Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Curtis E
authors.initials: CE
authors.lastname: Grace
authors.affiliation: Department of Pediatrics, Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Tori L
authors.initials: TL
authors.lastname: Schaefer
authors.affiliation: Department of Pediatrics, Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Skelton
authors.affiliation: Department of Nutrition, University of North Carolina, Greensboro, NC, USA.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Erikson
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.affiliation: Department of Pediatrics, Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Williams
keywords: Manganese; barren cage rearing; corticosterone; dopamine; norepinephrine; serotonin; shallow water stress