Journal
NEUROBIOLOGY OF DISEASE
Volume 37, Issue 1, Pages 130-140Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2009.09.016
Keywords
Nutrition; Thermogenesis; Anxiety; Seizure; Neuropeptides; Haploinsufficiency; PAM
Categories
Funding
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R01HD039708] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK032949] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [P50MH060451] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS045231, T32NS041224] Funding Source: NIH RePORTER
- NICHD NIH HHS [R01 HD039708-08] Funding Source: Medline
- NIDDK NIH HHS [R01 DK032949-26, R01 DK032949] Funding Source: Medline
- NIMH NIH HHS [P50 MH060451-07] Funding Source: Medline
- NINDS NIH HHS [R01 NS045231-04, T32 NS041224-04, T32 NS041224] Funding Source: Medline
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Mammalian genomes encode only a small number of cuproenzymes. The many genes involved in coordinating copper uptake, distribution, storage and efflux make gene/nutrient interactions especially important for these cuproenzymes Copper deficiency and copper excess both disrupt neural function. Using mice heterozygous for peptidylglycine alpha-armdating monooxygenase (PAM), a cuproenzyme essential for the synthesis of many neuropeptides. we identified alterations in anxiety-like behavior, thermoregulation and seizure sensitivity. Dietary copper supplementation reversed a subset of these deficits. Wildtype mice maintained on a marginally copper-deficient diet exhibited some of the same deficits observed in PAM(+/-) mice and displayed alterations in PAM metabolism. Altered copper homeostasis in PAM(+/-) mice suggested a role for PAM in the cell type specific regulation of copper metabolism Physiological functions sensitive to genetic limitations of PAM that are reversed by supplemental copper and mimicked by copper deficiency may serve as indicators of marginal copper deficiency. (C) 2009 Elsevier Inc. All rights reserved.
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