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Variations in Dietary Copper Alter Physiological and Behavioral Function
Author(s) -
BousquetMoore Danielle,
Eipper Betty,
Prohaska Joseph,
Mains Richard
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.231.5
Subject(s) - vasoconstriction , endocrinology , medicine , chemistry , wild type , knockout mouse , elevated plus maze , neuropeptide , biochemistry , anxiety , receptor , gene , mutant , psychiatry
Post‐translational α‐amidation by peptidyglycine α‐amidating monooxygenase (PAM), a Cu‐dependent enzyme, is required for the synthesis of many neuropeptides. Homozygous deletion of PAM is lethal and mice heterozygous for PAM (PAM +/− ) exhibit decreased peptide amidation, increased anxiety‐like behavior, decreased cold‐induced vasoconstriction and increased sensitivity to pentylenetetrazole (PTZ)‐induced seizures. Dietary and genetic limitations to Cu availability result in phenotypes similar to those observed in PAM +/− mice. We tested the hypotheses that increased dietary Cu could ameliorate deficits identified in PAM +/− mice and decreased dietary Cu could cause similar deficits in wildtype (WT) mice. PAM +/− and WT mice were supplemented with Cu (14d; 70 ppm Cu in drinking water), fed a Cu deficient diet (9 wk; Harlan Teklad 80388) or controls. As assessed in the elevated zero maze, anxiety‐like behavior was sensitive to Cu supplementation in PAM +/− mice and to Cu depletion in WT mice. Laser Doppler monitoring of tail blood flow in cold‐exposed mice revealed the ability of Cu supplementation to restore vasoconstriction in PAM+/‐ mice and Cu depletion to impair vasoconstriction in WT mice. Cu deficiency increased seizure sensitivity of WT mice (PTZ; 30 mg/kg ip). Serum levels of PAM activity rose in Cu deficiency and fell following Cu supplementation. Cu availability may affect similar parameters in man. Grant Funding Source National Research Service Award from the National Institute of Mental Health