Rodent brain and heart catecholamine levels are altered by different models of copper deficiency

Abstract

Limiting dopamine beta-monooxygenase results in lower norepinephrine (NE) and higher dopamine (DA) concentrations in copper-deficient Cu- tissues compared to copper-adequate Cu+ tissues. Mice and rat offspring were compared to determine the effect of differences in dietary copper Cu deficiency started during gestation or lactation on catecholamine, NE and DA, content in brain and heart. Holtzman rat and Hsd:ICR (CD-1) outbred albino mouse dams were fed a Cu- diet and drank deionized water or Cu supplemented water. Offspring were sampled at time points between postnatal ages 12 and 27. For both rat and mouse Cu- tissue, NE and DA changes were greater at later ages. Though Cu restriction began earlier in rats than mice in the gestational model, brain NE reduction was more severe in Cu- mice than Cu- rats. Cardiac NE reduction was similar in Cu- rodents in the gestation models. In the lactation model, mouse catecholamines were altered more than rat catecholamines. Furthermore, following lactational Cu deficiency Cu- mice were anemic and exhibited cardiac hypertrophy, Cu- rats displayed neither phenotype. Within a species, changes were more severe and proportional to the length of Cu deprivation. Lactational Cu deficiency in mice had greater consequences than in rats.

Fig. 1

Effects of Cu deficient dietary treatment during G or L on liver Cu and hemoglobin. (A) and (C) Suckling mice at P12 and Post Weanling at P27 were sampled. Each bar represents the mean ± SEM (n=4–7). (B) and (D) Suckling rats at P13 or P14 and Post Weanling at P21 or P24 were sampled. Each bar represents the mean ± SEM (n=4). Significantly different values are denoted by unlike lower case letters. Data were analyzed by factorial ANOVA and significant interactions were compared by Fisher’s PLSD, α=0.05.

Fig. 2

Effects of Cu deficient dietary treatment during G or L on brain Cu and cardiac hypertrophy (heart weight/body weight). (A) and (C) Suckling mice at P12 and Post Weanling at P27 were sampled. Each bar represents the mean ± SEM (n=4–7). (B) and (D) Suckling rats at P13 or P14 and Post Weanling at P21 or P24 were sampled. Each bar represents the mean ± SEM (n=4). Significantly different values are denoted by unlike lower case letters. Data were analyzed by factorial ANOVA and significant interactions were compared by Fisher’s PLSD, α =0.05.

Fig. 3

Effects of Cu deficient dietary treatment during G or L on medulla/pons (brain) NE and DA levels. (A) and (C) Suckling mice at P12 and Post Weanling at P27 were sampled. Each bar represents the mean ± SEM (n=4–7). (B) and (D) Suckling rats at P13 or P14 and Post Weanling at P21 or P24 were sampled. Each bar represents the mean ± SEM (n=4). Significantly different values are denoted by unlike lower case letters. Data were analyzed by factorial ANOVA and significant interactions were compared by Fisher’s PLSD, α =0.05.

Fig. 4

Effects of Cu deficient dietary treatment during G or L on heart NE and DA levels. (A) and (C) Suckling mice at P12 and Post Weanling at P27 were sampled. Each bar represents the mean ± SEM (n=4–7). (B) and (D) Suckling rats at P13 or P14 and Post Weanling at P21 or P24 were sampled. Each bar represents the mean ± SEM (n=4). Significantly different values are denoted by unlike lower case letters. Data were analyzed by factorial ANOVA and significant interactions were compared by Fisher’s PLSD, α =0.05.