Maternal zinc deficiency impairs brain nestin expression in prenatal and postnatal mice

INTRODUCTIONZinc is essential for normal brain development,evidenced by the fact that zinc deficiency in lactating mothers is characterized by a high incidence ofneuroanatomical maiformatinns and functional abnormalities in suckling offspring[1-3]. By colltrast,relatively little is known about the relationship be{tween maternal zinc nutrition and fetal brain development[2, 4, 5]. Dvergsten et al[6-81 investigated theeffects of maternal zinc deficiency on postnatal development of the rat ce…     

Long-term effects of lactational zinc deficiency on bone mineral composition in rats fed a commercially modified Luecke diet

The purpose of this study was threefold: 1. to determine the long-term effects of interactions between lactational zinc deficiency and gender on bone mineral composition in repleted rat offspring, 2. to determine the nutritional efficacy of the second of two commercially designed, modified Luecke diets (ML2) during the gestational and lactational stress, and 3. determine the ultratrace element contents of Ralston Rodent Laboratory Chow #5001. The ML2 basal diet, based on dextrose, sprayed egg white, and corn oil contained 0.420 μg Zn/g, was supplemented with Zn (as zinc acetate) at 0 (diet 0ML2) or 30 (diet 30ML2) μg/g, and was mixed and pelleted commercially. all rat dams were fed the 30ML2 diet ad libitum during gestation. Beginning at parturition, the dams were fed either the 1. 0ML2, 2. 30ML2 (food restricted), or 3. 30ML2 (ad libitum) diets. All pups were fed the 30ML2 diet ad libitum from 23 to 40 d of age. From d 40 to 150, all pups were fed Ralston Rodent Laboratory Chow. The 30ML2 diet was found to be nutritionally efficacious; litter size and pup growth were normal and pup mortality was only 1.2%. Pups (ZD) with access to the 0ML2 diet until 23 d of age and nursed by dams fed the 0ML2 diet, when compared to pups (PF) fed restricted amounts of the 30ML2 diet, exhibited increased mortality and decreased concentrations of tibial zinc but no change in growth. Inadequate zinc nutriture during infancy, despite postlactational zinc repletion, induced imbalances in adult bone mineral metabolism. Thus, at 150 d of age, the ZD pups exhibited increased levels of bone P and Mg and decreased concentrations of K as compared to the PF pups.     

Marginal zinc deficiency increases oxidative DNA damage in the prostate after chronic exercise

Approximately 12% of Americans do not consume the recommended level of zinc and could be at risk for marginal zinc deficiency. Zinc functions in antioxidant defense and DNA repair and could be important for prostate health. We hypothesized that marginal zinc deficiency sensitizes the prostate to oxidative stress and DNA damage. Rats were fed a zinc-adequate (ZA; 30 mg Zn/kg) or marginally zinc-deficient (MZD; 5–6 mg Zn/kg) diet for 6 weeks. MZD increased p53 and PARP expression but no change in 8-hydroxy-2′-deoxyguanosine levels was detected. To examine the susceptibility to exogenous oxidative stress, rats fed a ZA or MZD diet were assigned to exercising (EXE) or sedentary (SED) groups for 9 weeks. MZD or EXE alone did not affect oxidative DNA damage in the prostate; however, combined MZD + EXE increased DNA damage in the dorsolateral lobe. PARP and p53 expression was not further induced with MZD + EXE, suggesting that MZD interferes with DNA repair responses to stress. Finally, the addition of phytase to the MZD diet successfully restored zinc levels in the prostate and decreased DNA damage back to ZA levels. Overall, this study suggests that marginal zinc deficiency sensitizes the prostate to oxidative stress and demonstrates the importance of maintaining optimal zinc nutrition in physically active populations.     

Maternal zinc deficiency reduces NMDA receptor expression in neonatal rat brain, which persists into early adulthood

Prenatal and early postnatal zinc deficiency impairs learning and memory and these deficits persist into adulthood. A key modulator in this process may be the NMDA receptor; however, effects of zinc deficiency on the regulation of NMDA receptor activity are not well understood. Female Sprague-Dawley rats were fed diets containing 7 (zinc deficient, ZD), 10 (marginally zinc deficient, MZD) or 25 (control) mg Zn/g diet preconception through postnatal day (PN) 20, at which time pups were weaned onto their maternal or control diet. Regulation of NMDA receptor expression was examined at PN2, PN11, and PN65. At PN2, expression of whole brain NMDA receptor subunits NR1, NR2A, and NR2B was lower in pups from dams fed ZD and MZD compared to controls, as analyzed using relative RT-PCR and immunoblotting. At PN11, whole brain and hippocampi NR1, NR2A, NR2B and PSA-NCAM (polysialic acid-neural cell adhesion molecule) expression and the number of PSA-NCAM immunoreactive cells were lower in pups from dams fed ZD compared to controls. Whole brain brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) concentrations were lower in pups from dams fed ZD or both low zinc diets, respectively. Whole brain NR1 expression remained lower in previously zinc-deficient rats at PN65. These data indicate potential mechanisms through which developmental zinc deficiency can impair learning and memory later in life.     

Effects of marginal zinc deficiency on microtubule polymerization in the developing rat brain

One of the possible mechanisms that has been proposed to underlie the deleterious effects of zinc deficiency on brain development is an impairment in the normal formation of the cytoskeletal network. In the current study, in vivo microtubule polymerization was characterized in brain supernatant fluids, from 20-d-old pups whose dams were fed diets containing control (50 micrograms zinc/g) or marginal levels of zinc (10 micrograms zinc/g) throughout pregnancy and lactation. Pup brain and body weights were similar between the groups; however, plasma zinc concentrations were lower (27%) in pups fed the marginal zinc diet than in controls. Tubulin concentrations in 100,000 g brain supernates were similar between the groups; however, tubulin polymerization in the brain supernates was significantly lower in pups fed the marginal zinc diet compared to controls. Primarily, the early events of polymerization were affected; the lag period of the reaction was doubled, and the initial velocity was slower (26%) in supernates from pups fed the marginal zinc diet than in controls. These findings support the idea that some of the negative effects of marginal zinc deficiency on brain development and function may be mediated by an alteration in microtubule formation.     

Inhibitory effect of selenium and change of glutathione peroxidase activity on rat glioma

The inhibitory effect of selenium (Se) and change of glutathione peroxidase activity during the development of brain tumors was investigated in Wistar rats. Four rat groups classified to match by age and weight were fed a diet containing 0, 0.5, 2.0, and 4.0 μg Se/g. After 6 wk, the rats were injected with 3×10⁶ C₆ cells into the right frontal lobe parenchyma. Survival was significantly longer in the 0.5 and 2.0 μg Se/g groups than in the Se-free and 4.0 μg Se/g groups. The activity of glutathione peroxidase after development of tumors was significantly higher in the high Se group at 18 and 30 d.     

Effect of dietary caffeine and zinc on the activity of antioxidant enzymes,zinc, and copper concentration of the heart and liver in fast-growing rats

The purpose of this study was to determine the relationship between concentrations of Zn and Cu and the activities of superoxide dismutase and glutathione peroxidase in the heart and liver of young rat pups whose dams were fed a diet supplemented with caffeine and/or Zn. Four groups of dams with their newborn pups were fed one of the following diets for 22 d: 20% protein basal diet; the basal diet supplemented with caffeine (2 mg/100 body wt); the basal diet supplemented with Zn (300 mg/kg diet); or the basal diet supplemented with caffeine plus Zn. The Cu levels in the livers of the pups were decreased by maternal intake of the caffeine and Zn diet. The maternal intake of the caffeine diet increased Mn-superoxide dismutase (MnSOD) activity and Cu, Zn-superoxide dismutase (CUZnSOD) in the heart of the pups. On the other hand, the activity of Cu,ZnSOD was significantly reduced in the liver of pups whose dams consumed a caffeine, Zn, or caffeine plus Zn diet. Cu, ZnSOD activity in the liver of the pups seems to be correlated with Cu levels in the tissue. Selenium-dependent glutathione peroxidase (GSH-Px) activities in the heart and liver showed no difference among the groups. The effect of dietary caffeine and/or Zn on the activity of antioxidant enzymes in the heart and liver were different in young rats. The activities of these enzymes in the heart were lower than in the liver of 22-d-old rats. Our experiments indicate that the heart has limited defenses against the toxic effects of peroxides when compared to the liver.     

Interaction between nickel and iron in the rat

The interaction between nickel and iron was confirmed in rat metabolism. In a fully-crossed, two-way, three by four, factorially designed experiment, female weanling rats were fed a basal diet supplemented with iron at 0, 25, 50, and 100 μg/g and with nickel at 0, 5, and 50 μg/g. The basal diet contained about 10 ng of nickel and 2.3 μg of iron/g. After nine weeks, dietary iron affected growth, hematocrit, hemoglobin, plasma cholesterol, and in liver affected total lipids, phospholipids, and the contents of copper, iron, manganese, and zinc. By manipulating the iron content of the diet, effects of dietary nickel were shown in rats that were not from dams fed a nickel-deprived diet. Nickel affected growth, hematocrit, hemoglobin, plasma alkaline phosphatase activity, plasma total lipids, and in liver affected total lipids, and the contents of copper, manganese, and nickel. The interaction between nickel and iron affected hematocrit, hemoglobin, plasma alkaline phosphatase activity, and plasma phospholipids, and in liver affected size, content of copper, and perhaps of manganese and nickel. In severely iron-deficient rats, the high level of dietary nickel partially alleviated the drastic depression of hematocrit and hemoglobin, and the elevation of copper in liver. Simultaneously, high dietary nickel did not increase the iron level in liver and was detrimental to growth and appearance of severely iron-deficient rats. In nickel-deprived rats fed the borderline iron-deficient diet (25 μg/g) hematocrit and hemoglobin also were depressed. However, 5 μg Ni/g of diet were just as effective as 50 μg Ni/g of diet in preventing those signs of nickel deprivation. The findings in the present study suggested that nickel and iron interact with each other at more than one locus.     

Effects of germanium and silicon on bone mineralization

The chemical properties of Ge are similar to Si. This study investigated whether Ge can substitute for, or is antagonistic to, Si in bone formation. Sixty male weanling Sprague-Dawley rats were randomly assigned to treatment groups of 12 and 6 in a 2×4 factorially arranged experiment. The independent variables were, per gram fresh diet, Si (as sodium metasilicate) at 0 or 25 μg and Ge (as sodium germanate) at 0, 5, 30 or 60 μg. Results confirmed that Ge does not enhance Si deprivation and provided evidence that Ge apparently can replace Si in functions that influence bone composition. When Si was lacking in the diet, calcium and magnesium concentrations of the femur were decreased; this was reversed by feeding either Ge and/or Si. Similar effects were found for zinc, sodium, iron, manganese, and potassium of vertebra. There were some responses to Si deprivation that Ge could not reverse: Ge did not increase femur copper, sodium, or phosphorus or decrease molybdenum of vertebra, effects that were eveked by Si supplementation. Additionally, some findings suggested that 60 μg Ge/g diet could be a toxic intake for the rat. On the other hand, some responses induced by Ge indicate that this element may be acting physiologically other than as a substitute for Si. Germanium itself affected bone composition. Germanium supplementation decreased Si and molybdenum in the femur and increased DNA in tibia. Regardless of the amount of Si fed, animals fed 30 μg Ge/g diet had increased tibial DNA compared to animals fed 0 or 60 μg Ge; however, tibial DNA of animals fed 30 μg Ge was not statistically different from those animals fed 5 μg Ge. Thus, Ge may be of nutritional importance.     

Inducibility and amounts of metallothionein as influenced by cadmium and zinc in the developing rat

Information on the accumulation and/or depletion of Zn in metallothionein (MT) of rat fetus, rat pup, and maternal rat liver at various ages was obtained with pregnant rats fed a basal casein diet or this diet plus either 100 ppm Zn or 50 ppm Cd. Rats fed each of the respective diets were sacrificed on 12, 16, and 20 d of gestation and 0, 7, 14, and 28 d post-partum. No Cd was detected in the placenta or fetal tissue and the Cd did not affect the accumulation of Zn in the fetal MT, but it did increase the Zn content in liver MT of the dams. Very little Zn in MT was found on day 12 of gestation, but Zn rapidly increased in MT to a maximum at time of birth. The accumulation of Zn in MT was independent of the diet for the fetuses, but the Zn accumulation in the dam and pup tissues was diet dependent. In order to study age-dependent difference in the inducibility of MT, newborn, 5-week-old, or 24-week-old rats were injected with zinc at the levels of 0, 3, 6, or 9 mg/kg and 5 h later injected with³⁵S-cystine. In rats sacrificed 1 h later, the amount of radioactivity in liver MT demonstrated that this protein in older animals was more readily induced by Zn than in younger animals.     

Sodium vanadate toxicity in adult and developing rats

The toxic effect of vanadium (sodium metavanadate) during pregnancy and lactation was studied by feeding vanadium to pregnant, Sprague-Dawley rats at levels of 1 (control) or 75 μg V/g diet through d 21 postpartum, at which time they were killed. Vanadium-fed dams had lower food intakes and weight gains than controls during pregnancy. Survival until d 21 postpartum was significantly lower in the vanadium pups compared to controls. In addition, the surviving pups gained less weight than control pups, despite similar birth weights. On a relative body weight basis, vanadium pups had larger livers, brains, and testes than controls, suggesting that these animals were developmentally delayed. Vanadium dams and pups had higher concentrations of hepatic vanadium than controls. Vanadium pups also had higher concentrations of hepatic zinc than control pups. Maternal hepatic zinc concentrations were not affected by diet. Also, no significant differences in hepatic iron, copper, or manganese concentrations were observed for either dams or pups. Hepatic thiobarbituric acid reactivity was higher in whole cell and isolated mitochondria for vanadium dams and pups than for control dams and pups, indicating that these animals may have had higher levels of lipid peroxidation. This idea was supported by the observation of lower concentrations of reduced glutathione in the livers of vanadium pups compared to controls. In contrast, kidney and brain glutathione levels were not affected by diet. In conclusion, animals during periods of rapid growth are susceptible to vanadium toxicity, and increased lipid peroxidation may be one factor underlying this toxicity.     

Influence of maternal mineral deficiency on the hepatic metallothionein and zinc in newborn rats

The effects of maternal Zn, Cu, or Fe deficiencies during late gestation on hepatic levels of metals and metallothionein (MT) and the binding of Zn and Cu to protein fractions were investigated in newborn rats. Timed pregnant rats were fed one of the following diets: Zn deficient (Zn-D), Cu-D, Fe-D, or control from day 12 of gestation until birth. The specific nutritional deficiency status of the dams was confirmed by low plasma levels of the deficient metal. Livers from pups were analyzed for MT, metal content, and metal-protein binding. Maternal Zn-D resulted in a greater than 50% reduction of hepatic MT levels in pups, whereas Cu-D and Fe-D had no significant effects. Pups in each deficient group showed a significant decrease in the hepatic levels of the respective metals. Fractionation of hepatic cytosols from the pups by Sephadex G-75 gel filtration showed that in both Fe-D and Cu-D pups the respective metals were depleted from the high molecular weight protein fraction, whereas in Zn-D pups the Zn was depleted mainly from the MT fraction (Ve/V0 approximately 2). Incorporation of [35S] cysteine into MT fractions was significantly lower in Zn-D pups as compared with control pups. These results indicate that there is a specific effect of the maternal Zn-D on the hepatic storage of Zn as MT in newborn rats.     

Associations of Socio-demographic and Behavioral Variables with Hair Zinc of Vancouver Preschoolers

Marginal zinc deficiency (MZD) exists in children of industrialized societies and impairs growth and development. MZD is believed to be one of the most common deficiencies, even though there is no data available on its global prevalence. This is partly because of the lack of sensitivity and specificity of serum zinc, the most commonly used biomarker of zinc status, to detect MZD. In children, MZD is always accompanied by a decrease in hair zinc. This cross-sectional study was designed to explore if there are any associations between some socio-demographic and behavioral variables with hair zinc status in an attempt to understand the social determinants of MZD and the profile of at risk children. Our citywide survey (n = 719) indicated a mean hair zinc of 116 ± 43 μg/g with 17% below the cutoff. Logistic regression analysis indicated that age, maternal education, number of adults at home, being described as “eating unhealthy”, and Child Behavior Questionnaire scores of “activity level” as the significant predictors of hair zinc status. Our study provides important information on the hair zinc status of Vancouver preschoolers and some factors in children and their environment associated with hair zinc, which may help in better understanding of hair zinc as a biomarker of MZD.     

Zinc Nutritional Status in Adolescents with Down Syndrome

Studies have evidenced that zinc metabolism is altered in presence of Down syndrome, and zinc seems to have a relationship with the metabolic alterations usually present in this syndrome. In this work, the Zn-related nutritional status of adolescents with Down syndrome was evaluated by means of biochemical parameters and diet. A case–control study was performed in a group of adolescents with Down syndrome (n = 30) and a control group (n = 32), of both sexes, aged 10 to 19 years. Diet evaluation was accomplished by using a 3-day dietary record, and the analysis was performed by the NutWin program, version 1.5. Antropometric measurements were performed for evaluation of body composition. The Zn-related nutritional status of the groups was evaluated by means of zinc concentration determinations in plasma and erythrocytes, and 24-h urinary zinc excretion, by using the method of atomic absorption spectroscopy. The diet of both groups presented adequate concentrations of lipids, proteins, carbohydrates, and zinc. The mean values found for zinc concentration in erythrocytes were 49.2 ± 8.5 μg Zn/g Hb for the Down syndrome group and 35.9 ± 6.1 μg Zn/g Hb for the control group (p = 0.001). The average values found for zinc concentration in plasma were 67.6 ± 25.6 μg/dL for the Down syndrome group and 68.9 ± 22.3 μg/dL for the control group. The mean values found for zinc concentration in urine were 244.3 ± 194.9 μg Zn/24 h for the Down syndrome group and 200.3 ± 236.4 μg Zn/24 h for the control group. Assessment of body composition revealed overweight (26.7%) and obesity (6.6%) in the Down syndrome group. In this study, patients with Down syndrome presented altered zinc levels for some cellular compartments, and the average zinc concentrations were low in plasma and urine and elevated in erythrocytes.     

Change in apparent and true absorption and retention of dietary zinc with age in rats

Two groups of 16 rats each were fed the same diet with 12.9 ppm Zn. Nine days after each animal was injected with⁶⁵Zn for assessing fecal zinc of endogenous origin, zinc intake and excretion were determined for a six-day period at the age of about five (group I) and nine (II) weeks. At mean growth rates of 5.1 and 5.2 g/day, food consumption per gram of gain was 2.01 g in group I vs 2.86 g in II. Overall, zinc retention amounted to 21 vs 25 μg Zn/g of gain. Apparent absorption averaged 92 vs 74% of Zn intake (132 vs 189 μg/day), while true absorption averaged 98 vs 92%. It was concluded that endogenous fecal zinc excretion was limited to the indispensable loss (F _em) in group I (7 μg/day), while it exceeded this minimum loss in group II (33 μg/day). True retention, which reflected total zinc utilization (true absorption times metabolic efficiency), was derived from apparent absorption plusF _em (11 μg/day for group II according to the greater metabolic body size of the rats). It averaged 98% of Zn intake in group I vs 80% in group II. The mean metabolic efficiency was 100% vs 87%. The conclusion was that these marked differences between age groups in utilizing the dietary zinc reflected the efficient homeostatic adjustments in absorption and endogenous excretion of zinc to the respective zinc supply status.     

Maternal deficiency of protein or protein and calories during lactation: effect upon CNS myelin subfraction formation in rat offspring.

The present study has examined the effects of maternal protein and protein-calorie deficiency during lactation on the development of CNS myelin subfractions in rat offspring. The offspring of both the protein and protein-calorie deficient rats had decreased brain and body weights, as well as delayed CNS myelination. Delayed active CNS myelination was demonstrated by the fact that 53-day-old nutritionally stressed pups incorporated significantly more [³H]leucine and [¹⁴C]glucose into all myelin subfractions than age-matched controls. Delayed myelination was also supported by the tremendous accretion of myelin proteins in the nutritionally deprived pups between 25 and 53 days of age. Despite the delayed active synthesis of myelin, the myelin deficit persisted in the offspring of protein deficient rats. These offspring had a deficiency of light + medium myelin throughout the study. At 17 days, both groups of nutritionally stressed rats had an excess of the high molecular weight proteins in heavy myelin. Heavy myelin from 17 day offspring of protein-calorie deficient rats had a deficiency of basic proteins, while that from the offspring of protein deficient rats had a deficiency of proteolipid protein. The protein composition of all myelin subfractions was normal at 53 days.     

Effects of α-methylphenylalanine plus phenylalanine treatment during development on myelin in rat brain

The effects of hyperphenylalaninemia induced by treatment with -methylphenylalanine (MPA) plus phenylalanine (PHE) on body and brain weight, on myelin and synaptosome formation, and on the lipids and fatty acids of myelin were studied in rats. The administration of MPA (2.4 mol/g body wt) plus PHE (2.6 mol/g body wt) for 25 and 35 days beginning on the fifth postnatal day did not affect brain development. On doubling the dosage of PHE, body and brain weights and myelin yields were significantly lowered. The lipid composition of myelin from the brains of treated animals was largely unaffected; however, the concentration of sulfatides was significantly reduced. Unsaturated fatty acid levels in myelin from hyperphenylalaninemic rat brains were reduced while long-chain fatty acids were unaffected. We conclude that as in hyperphenylalaninemia induced by other methods, MPA+PHE treatment impairs body and brain growth, reduces myelin formation, and causes inhibition of fatty acid desaturation in the brain.     

Comparative effect of amidated pectin and psyllium on cholesterol homeostasis in rats

The effects of amidated pectin and psyllium on serum, hepatic and faecal cholesterol concentration were compared in female rats fed diets supplemented with palm fat and cholesterol at 50 and 10 g/kg, respectively. Control rats were fed a diet supplemented with cellulose at 60 g/kg. In treated rats, cellulose was replaced with either amidated pectin or psyllium. Amidated pectin and psyllium intake significantly decreased serum cholesterol from 3.41 μmol/ml (control) to 1.68 and 2.04 μmol/ml, respectively, and hepatic cholesterol from 31.9 μmol/g (control) to 7.2 and 9.0 μmol/g, respectively. Histology with lipid-staining Sudan Black B revealed that liver tissue from control rats was infiltrated with lipids, but staining was absent in livers of treated rats. No hepatic pathophysiology was apparent in treated rats. Amidated pectin and psyllium intake significantly increased faecal fat content. Faecal cholesterol content was significantly increased in rats that were fed amidated pectin, and non-significantly increased in rats that were fed psyllium. Body weight and food intake did not differ among treatment groups. In conclusion, amidated pectin, a novel sequestrant of sterols, demonstrated a similar effect on rat serum and hepatic cholesterol concentration to psyllium, which is a well-established hypocholesterolaemic agent.     

Assessing the effects of low boron diets on embryonic and fetal development in rodents using in vitro and in vivo model systems

To date, boron (B) essentiality has not been conclusively shown in mammals. This article summarizes the results of a series of in vitro and in vivo experiments designed to investigate the role of B in mammalian reproduction. In the first study, rat dams were fed either a low (0.04 μg B/g) or an adequate (2.00 μg B/g) B diet for 6 wk before breeding and through pregnancy; reproductive outcome was monitored on gestation day 20. Although low dietary B significantly lowered maternal blood, liver, and bone B concentrations, it had no marked effects on fetal growth or development. The goal of the second study was to assess the effects of B on the in vitro development of rat postimplantation embryos. Day 10 embryos collected from dams fed either the low or adequate B diets for at least 12 wk were cultured in serum collected from male rats exposed to one of the two dietary B treatments. Dams fed the low B diet had a significantly reduced number of implantation sites compared to dams fed the B-adequate diet. However, embryonic growth in vitro was not affected by B treatment. The aim of study 3 was to define the limits of boric acid (BA) toxicity on mouse preimplantation development in vitro. Two-cell mouse embryos were cultured in media containing graded levels of BA (from 6 to 10,000 μM). Impaired embryonic differentiation and proliferation were observed only when embryos were exposed to high levels of BA (>2000 μM), reflecting a very low level of toxicity of BA on early mouse embryonic development. Study 4 tested the effects of low (0.04 μg B/g) and adequate (2.00 μg B/g) dietary B on the in vitro development of mouse preimplantation embryos. Two-cell embryos obtained from the dams were cultured in vitro for 72 h. Maternal exposure to the low B diet for 10, 12, and 16 wk was associated with a reduction in blastocyst formation, a reduction in blastocyst cell number, and an increased number of degenerates. Collectively, these studies support the concept that B deficiency impairs early embryonic development in rodents.