Brain copper

Genetic and nutritional studies have illustrated the essential nature of copper for normal brain function. Deficiency of copper during the foetal or neonatal period will have adverse effects both on the formation and the maintenance of myelin (Kuo et al., 2001 Lee et al., 2001 Sun et al., 2007 Takeda and Tamana, 2010). In addition, various brain lesions will occur in many brain regions, including the cerebral cortex, olfactory bulb, and corpus striamm. Vascular changes have also been observed. It is also of paramount importance that excessive amounts of copper do not occur in cells, due to redox mediated reactions such that its level within cells must be carefully controlled by regulated transport mechanisms. Copper serves as an essential cofactor for a variety of proteins involved in neurotransmitter synthesis, e.g. dopamine P-hydroxylase, which transforms dopamine to nor-adrenahne, as well as in neuroprotection via the Cu/Zn superoxide dismutase present in the cytosol. Excess free copper is however deleterious for cell metabolism, and therefore intracellular copper concentration is maintained at very low levels, perhaps as low as 10 M. Brain copper homeostasis is still not well understood. 

Pinder Is dopamine a substrate for caeruloplasmin If so, does the enzyme play a role in mediating dysfunctions of brain copper metabolism such as in Wilson s disease, particularly since dopaminergic deficiency is involved in the symptomatically related condition of Parkinsonism ... 

A symptom of copper deficiency in man and animals is seizures, which subside with copper supplementation [135, 305-310]. Seizures following treatment with tremor-inducing drugs are accompanied by a concomitant reduction in brain copper levels [311-314]. Also, brain norepinephrine and epinephrine concentrations are reduced in association with seizures [1, 311, 315-320]. This latter observation is particularly relevant, since two copper-dependent enzymes are required for the synthesis of norepinephrine and epinephrine. 

It has been suggested that a major portion of brain copper is in the form of Cu Zn SOD [330] and that seizures may be due to a lack of superoxide disproportionation in the brain [331]. Since copper complexes in general have... 

Faa, G., Lisci, M., Caria, M. P., Ambu, R, Sciot, R. N., Nurchi, V. M. Silvagni, R, Diaz, A, Crisponi, G. (2001) Brain copper, iron, magnesium, zinc, calcium, sulfin and phosphorus storage in Wilson s disease. / Trace Elem Med Biol, 15, 155-160. 

Monnot, A.D., Behl, M., Ho, S., et ah, 2011. Regulation of brain copper homeostasis by the brain barrier systems effects of Fe-overload and Fe-deficiency. Toxicol. Appl. Pharmacol. 256, 249-257. 

Copper. AH human tissues contain copper. The highest amounts are found in the Hver, brain, heart, and kidney (102). In blood, plasma and erythrocytes contain almost equal amounts of copper, ie, ca 110 and 115 mg/100 mL, respectively. 

Copper-64 is one of the metals used to study brain activity. Its decay constant is 0.0546 h-1. If a solution containing 5.00 mg of Cu-64 is used, how many milligrams of Cu-64 remain after eight hours ... 

Ceballos-Picot, I., Nicole, A., Briand, P., Grimber, G., Delacourte, A., Defossez, A., Javoy-Agid, F., Lafon, M., Blouin, J.L. and Sinet, P.M. (1991). Neuronal-specific expression of human copper-zinc superoxide dismutase gene in transgenic mice animal model of gene dosage effects in Down s syndrome. Brain Res, 552, 198-214. 

H. Porter and S. Ainsworth, The isolation of the copper-containing protein cerebrocuprein I from normal human brain. J. Neurochem. 5, 91-98 (1959). 

Wilson s disease is an autosomal recessive disorder characterized by the accumulation of copper in liver and brain [21]. Hepatic involvement may result in liver cirrhosis and hepatic cancer. The deposition of copper in the basal ganglia results in a variety of movement disorders, including... 

Adults require 1-2 mg of copper per day, and eliminate excess copper in bile and feces. Most plasma copper is present in ceruloplasmin. In Wilson s disease, the diminished availability of ceruloplasmin interferes with the function of enzymes that rely on ceruloplasmin as a copper donor (e.g. cytochrome oxidase, tyrosinase and superoxide dismutase). In addition, loss of copper-binding capacity in the serum leads to copper deposition in liver, brain and other organs, resulting in tissue damage. The mechanisms of toxicity are not fully understood, but may involve the formation of hydroxyl radicals via the Fenton reaction, which, in turn initiates a cascade of cellular cytotoxic events, including mitochondrial dysfunction, lipid peroxidation, disruption of calcium ion homeostasis, and cell death. 

Two inherited human diseases that represent abnormal copper metabolism are Menkes syndrome and Wilson s disease. Menkes syndrome, with symptoms similar to those of copper deficiency, is characterized by a progressive brain disease, abnormally low copper concentrations in liver and other tissues, and diminished ability to transfer copper across the absorptive cells of the intestinal mucosa (USEPA 1980 Aaseth and Norseth 1986). Wilson s disease (hepatolenticular degeneration) is the only significant example of copper toxicity in humans. Wilson s disease is an autosomal recessive disorder that affects normal copper homeostasis and is characterized by excessive... 

Human foods that are particularly rich in copper (20 to 400 mg Cu/kg) include oysters, crustaceans, beef and lamb livers, nuts, dried legumes, dried vine and stone fruits, and cocoa (USEPA 1980). In humans, copper is present in every tissue analyzed (Schroeder et al. 1966). A 70-kg human male usually contains 70 to 120 mg of copper (USEPA 1980). The brain cortex usually contains 18% of the total copper, liver 15%, muscle 33%, and the remainder in other tissues — especially the iris and choroid of the eye. Brain gray matter (cortex) has significantly more copper than white matter (cerebellum) copper tends to increase with increasing age in both cortex and cerebellum. In newborns, liver and spleen contain about 50% of the total body burden of copper (USEPA 1980). Liver copper concentrations were usually elevated in people from areas with soft water (Schroeder et al. 1966). Elevated copper concentrations in human livers are also associated with hepatic disease, tuberculosis, hypertension, pneumonia, senile dementia, rheumatic heart disease, and certain types of cancer (Schroeder et al. 1966). 

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