The effect of dietary zinc deficiency on the mossy fiber zinc content of the rat hippocampus. A microbeam PIXE study. Particle Induced X-Ray Emission

The effect of dietary zinc deficiency on the mossy fiber zinc content of the rat hippocampus was investigated using PIXE (Particle Induced X-Ray Emission) spectroscopy. Using the proton microbeam (60 X 60 microns), 2 mm line-scans were made on hippocampal sections and the data were expressed as absolute zinc concentrations. Values of 55 and 136 ppm (dry weight) were found for the mean background zinc level and the maximum mossy fiber zinc level, respectively, in animals fed a control diet containing 50 ppm zinc. Treatment of these animals with dithizone caused about 50% reduction in the maximum mossy fiber zinc level. Feeding a zinc-deficient diet for 28 days did not cause a decrease in the mossy fiber zinc level, however, feeding the zinc-deficient diet for 90 days reduced the maximum mossy fiber zinc level by about 30%. The results are discussed in relation to the behavioral abnormalities that have been observed in zinc-deficient animals.     

Gestational zinc deficiency amplifies the regulation of metallothionein induction in adult mice

To determine if prenatal zinc deficiency has a persistent effect on metallothionein (MT) regulation, Swiss-Webster mice were mated and fed a diet containing either control (100 micrograms Zn/g) or low levels of zinc (5 micrograms Zn/g) from Day 7 of gestation to parturition. After birth all mice were given the control diet. Liver zinc and MT levels were 50% lower in newborn pups from dams fed the low zinc diets than in control pups. In control pups, liver zinc and MT concentrations were relatively stable during the first week of postnatal life. In contrast, in pups prenatally deprived of zinc, liver levels of zinc and MT increased such that by Day 3 of postnatal life, the levels were not significantly different from controls. At Day 56, serum IgM concentrations were significantly lower in the low zinc offspring. Liver zinc concentrations in the two groups of mice were similar at Day 70 postnatal, and in both groups liver MT levels were below detection limits. However, when Day 70 mice were given zinc injections to stimulate MT synthesis, the prenatally zinc deprived offspring showed markedly higher liver MT levels than did control mice given similar injections, despite similar liver zinc concentrations in the two groups. These results show that prenatal zinc deficiency has pronounced effects on postnatal MT metabolism which can persist into adulthood.     

Chronic maternal dietary iodine deficiency but not thiocyanate feeding affects maternal reproduction and postnatal performance of the rat

Iodine deficiency disorders affect reproductive performance in the afflicted populations. Environmental iodine deficiency (ID) and goitrogens are important in their aetiology. We observed earlier that chronic maternal dietary ID but not goitrogen feeding altered the blood-brain barrier nutrient transport in adult rats. Whether similar differences exist in their effects on reproduction of dams and postnatal performance of the offspring has been assessed. Inbred, female, weaning WNIN rats were rendered hypothyroid by feeding for 8-12 weeks, a low iodine test diet or a control diet with added potassium thiocyanate (KSCN) (@ 25 mg/rat/day). Following mating with control males, they continued on their respective diets till their pups were weaned. Indices of reproductive performance such as percentage of conception, mortality of dams during pregnancy and parturition, litter size, and survival of pups till weaning were affected markedly by ID but not thiocyanate feeding. Neither ID nor thiocyanate feeding from conception or parturition affected their reproductive performance. Nevertheless, postnatal weight gain of pups was less in all the three ID groups but not thiocyanate fed dams. Rehabilitation of chronically ID pregnant dams from conception or parturition did not improve their pregnancy weight gain, litter size or birth weight of pups but decreased abortion and mortality of mothers during pregnancy and parturition. Rehabilitation improved the pups' postnatal weight gain but the effect was only moderate. Based on the results of the present study it may be suggested that maternal ID but not thiocyanate feeding affects reproductive performance and postnatal performance of their offspring.     

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.     

Regulation of the ontogeny of rat liver metallothionein mRNA by zinc

To investigate the role of metals in the regulation of the ontogenic expression of rat liver metallothionein (MT) mRNA, the concentrations of zinc, MT and MT mRNA were determined in livers of fetal and newborn rats from dams which were fed with a control or zinc-deficient or copper-deficient or iron-deficient diet from day 12 of gestation. The liver samples were analyzed for MT-mRNA levels using a mouse MT-I cRNA probe. Although the newborn hepatic levels of each metal (zinc or copper or iron) was specifically reduced corresponding to the respective mineral deficiencies, the hepatic concentrations of total MT and MT-I mRNA were significantly decreased only in pups born from zinc-deficient dams. Injection of the zinc-deficient newborn pups with 20 mg Zn as ZnSO4/kg restored with MT-I mRNA levels to slightly above control values within 5 h of injection. The hepatic zinc, MT and MT-I mRNA levels were observed to increase significantly in control fetal rat liver on days 17-21 of gestation but there were little changes in either zinc or MT in fetal livers from zinc-deficient dams during the late gestational period. The MT-I mRNA level also did not show an increase on days 18 and 20 of gestation in zinc-deficient fetal liver as compared to controls. These results demonstrate a direct role of zinc in hepatic MT gene expression in rat liver during late gestation. Immunohistochemical localization of MT using a specific antibody to rat liver MT showed that the staining for MT in zinc-deficient pup liver was mainly in the cytosol in contrast to the significant nuclear MT staining observed in control newborn rat liver. The results suggest that maternal zinc deficiency has a marked effect not only in decreasing the levels of hepatic MT and MT-I mRNA but also in the localization of MT in newborn rat liver.     

Responsiveness to kainate in young rats after 2-week zinc deprivation

On the basis of the evidence of the enhanced susceptibility to kainate-induced seizures in young rats fed a zinc-deficient diet for 4 weeks, the relationship between zinc release from hippocampal neuron terminals and seizure susceptibility was studied in young rats fed the zinc-deficient diet for 2 weeks. Timm’s stain, with which histochemically reactive zinc in the presynaptic vesicle is detected, was not attenuated in mossy fibers and other areas in the hippocampus after 2-week zinc deprivation, whereas the attenuation was observed after 4-week zinc deprivation. Extracellular zinc concentration was not also decreased after 2-week zinc deprivation, unlike the case after 4-week zinc deprivation. To check the capacity for zinc release from neuron terminals after 2-week zinc deprivation, the hippocampus was excessively stimulated with 100 mM KCl. The increase in extracellular zinc concentration of zinc-deficient group was significantly more than that of control group. These results suggest that zinc release from hippocampal neuron terminals is not affected by 2-week zinc deprivation. On the other hand, the latency in myoclonic jerks of zinc-deficient group was significantly shorter than in the control group after treatment with kainate, while the latency in clonic convulsions was not different between the two groups. Intracellular fura-2 signal, a calcium indicator, was significantly higher in the hippocampal CA3 areas of zinc-deficient group 4 s after delivery of kainate to dentate granule cells. These results suggest that susceptibility to kainate-induced seizures is altered prior to the decrease in extracellular zinc concentration and zinc release from neuron terminals in zinc-deficient young rats. The alteration of calcium signaling seems to be involved in the susceptibility in zinc deficiency.     

Comparative Effects of Ethanol and Malnutrition on the Development of Catecholamine Neurons: Changes in Neurotransmitter Levels

Abstract: The comparative effects of exposure to ethanol and malnutrition on the concentrations of tyrosine and catecholamines in whole brain and selected regions of brain have been studied in the developing rat. These animals were the offspring of optimally nourished rats (control pups), of rats fed a diet with 35% of the calories supplied by ethanol (ETOH pups), or of animals fed a diet calorically equivalent to the latter but lacking ethanol (iso-caloric, 1C pups). These diets were administered to dams either during the last week of gestation (prenatal) or during lactation (postnatal). Tyrosine levels were elevated prior to birth in the prenatal ETOH or IC pups or at 1 and 2 weeks of age in postnatal ETOH or 1C pups as compared with values found in the control offspring. Dopamine concentration in whole brain was significantly lower in prenatal ETOH pups than in prenatal IC pups at 3 weeks of age. Levels in the brains of postnatal ETOH pups were lower than control values, but not relative to animals exposed to 1C diet. Investigation of corpus striatum showed a significant decrease in dopamine concentration compared with control or IC pup values as a result of postnatal exposure to ethanol. Norepinephrine levels in the whole brain of prenatal ETOH pups were consistently 30–40% lower than either control or matched 1C pups during development. At 3 weeks of age, the norepinephrine levels in the hypothalamus of animals exposed to ethanol pre or postnatally were 30–60% lower than values in the corresponding region in either control or 1C pups. In the rat model described, ethanol caused a decrease in catecholamine levels, perhaps solely by affecting the norepinephrine neurons.     

Fetal and postnatal zinc restriction: sex differences in the renal renin-angiotensin system of newborn and adult Wistar rats

This study aimed to evaluate renal morphology and the renal renin-angiotensin system in 6- and 81-day-old male and female offspring exposed to zinc deficiency during fetal life, lactation and/or postnatal growth. Female Wistar rats were fed low- or control zinc diets from pregnancy to offspring weaning. Afterwards, offspring were fed a low- or a control zinc diet until 81 days of life. In 6- and/or 81-day-old offspring, we evaluated systolic blood pressure, renal morphology, renal angiotensin II and angiotensin 1-7 concentration, and AT1 and AT2 receptors and angiotensin-converting enzymes protein and/or mRNA expression. At 6 days, zinc-deficient male offspring showed decreased glomerular filtration areas, remodelling of renal arteries, greater number of renal apoptotic cells, increased levels of Angiotensin II, higher Angiotensin II/Angiotensin 1-7 ratio and increased angiotensin-converting enzyme 1, AT1 and AT2 receptors mRNA and/or protein expression. Exacerbation of the renal Ang II/AT1 receptor axis and remodelling of renal arteries were also observed in adult zinc-deficient male offspring. An adequate zinc diet during post-weaning life did not improve all the alterations induced by zinc deficiency in early stages of development. Female offspring would appear to be less sensitive to zinc deficiency with no increase in blood pressure or significant alterations in renal morphology and the renin-angiotensin system. Moderate zinc deficiency during critical periods of prenatal and postnatal development leads to early morphological renal alterations and to permanent and long-term changes in the renal renin-angiotensin system that could predispose to renal and cardiovascular diseases in adult life.     

Effects of prenatal dexamethasone on spatial learning and response to stress is influenced by maternal factors

The present study investigated the effect of prenatal dexamethasone (Dex) exposure on early perinatal events, hippocampal function, and response to stress. Pregnant rats received Dex in the evening water (2.5 microg/ml) or tap water (Veh) from gestational day 15 until delivery. On the day of parturition, pups were randomized, cross-fostered, and reduced to eight or nine per dam. Four groups resulted: Veh-Veh (offspring exposed to Veh in utero, rearing mother treated with Veh during gestation), Veh-Dex, Dex-Veh, and Dex-Dex. Spatial visual memory was evaluated with the Morris water maze. The corticosterone response to restraint stress was examined, and the expression of hippocampal glucocorticoid and mineralocorticoid receptors mRNA was determined by in situ hybridization. Exposure to Dex caused restlessness in mothers, low birth weights, and poor weight gain in the offspring. The Dex-Dex males had impaired spatial learning, inability to rapidly terminate the adrenocortical response to stress, and decreased hippocampal glucocorticoid receptor (GR) mRNA expression. In contrast, Dex-exposed animals reared by Veh-treated mothers had adequate spatial learning, enhanced glucocorticoid feedback, and increased hippocampal GR mRNA. We conclude that the environment provided by a healthy mother during the postnatal period can prevent the detrimental effects of prenatal Dex administration on cognition, GR mRNA expression of the hippocampus, and the quality of the stress response.     

Postnatal accumulation of zinc by the rat hippocampus

Timm's staining material has been detected in the rat hippocampus as early as day 1 postnatally. However, staining was diffuse and widespread and light granulation was observed only in the mossy fiber layer. By day 6 postnatally most diffuse staining had disappeared and the characteristic pattern of granulation had intensified in the mossy fiber layer. Pronounced staining of the mossy fibers became apparent from day 6. Electron microscopic autoradiography indicated that⁶⁵Zn injected intraperitoneally into suckling pups became localized largely in the axons and axon terminals of the mossy fiber layer in the CA3 and CA4 regions of the Horn of Ammon. In vitro studies with hippocampal slices have demonstrated that zinc is accumulated by an active transport system, but the kinetic characteristics of this uptake do not appear to alter with age. Zinc located intracellularly in the hippocampus appears to be associated mainly with large molecular weight ligands, with more than 75% of newly acquired zinc being bound to substances having molecular weights greater than 70,000 Daltons.     

Effect of hypothyroidism induced by propylthiouracil on ovarian function and structure in offspring from treated mothers (Rats)

The aim of the present study was to investigate the effects of hypothyroidism induced during the pre- and postnatal periods of life on ovarian function and structure in offspring (pups) 120 days of age. Three groups were used. In the prenatal group, treatment was given from conception to parturition. In the postnatal group, treatment was given from parturition to 25 days postpartum. Hypothyroidism was induced by administration of 0.1% 6-n-propyl-2-thiouracil (PTU) in the drinking water of mothers. Body weights of the offspring were measured weekly. In each group, ten offspring were sacrificed at 120 days of age. Postnatal PTU treated pups showed delay in eye opening, teething, fur development, and weaning (35-37 days) compared to control animals (28-30 days). Body weight of offspring in the postnatal PTU treatment group was significantly decreased (P < 0.001), while the prenatal PTU treatment group showed a significant increase (P < 0.0001) compared to control animals. There was a significant (P < 0.05) reduction in paired ovarian weight of offspring in the postnatal PTU treatment group compared to control animals. Diameter of the ovaries was not affected by any treatment. Regarding the morphometery, only offspring in the prenatal PTU treatment group showed a significant (P < 0.001) increase in the diameter of graafian follicles. No significant difference was observed in morphometery of the granulosa layer, primary, and developing follicles of control and all treated groups. Number of primary, developing, and graafian follicles of all the treated groups was similar to that of the control group. The corpora lutea of the postnatal PTU treated group contained a population of large numbers of luteal cells compared to the control group. The prenatal PTU treated group did not exhibit a profound effect on ovarian morphology, histology, and morphometery. No difference was found in the serum estradiol concentration of control and PTU treated groups. J. Exp. Zool. 293:407-413, 2002.     

Maternal Vitamin C Deficiency during Pregnancy Persistently Impairs Hippocampal Neurogenesis in Offspring of Guinea Pigs

While having the highest vitamin C (VitC) concentrations in the body, specific functions of VitC in the brain have only recently been acknowledged. We have shown that postnatal VitC deficiency in guinea pigs causes impairment of hippocampal memory function and leads to 30% less neurons. This study investigates how prenatal VitC deficiency affects postnatal hippocampal development and if any such effect can be reversed by postnatal VitC repletion. Eighty pregnant Dunkin Hartley guinea pig dams were randomized into weight stratified groups receiving High (900 mg) or Low (100 mg) VitC per kg diet. Newborn pups (n = 157) were randomized into a total of four postnatal feeding regimens: High/High (Control); High/Low (Depleted), Low/Low (Deficient); and Low/High (Repleted). Proliferation and migration of newborn cells in the dentate gyrus was assessed by BrdU labeling and hippocampal volumes were determined by stereology. Prenatal VitC deficiency resulted in a significant reduction in postnatal hippocampal volume (P<0.001) which was not reversed by postnatal repletion. There was no difference in postnatal cellular proliferation and survival rates in the hippocampus between dietary groups, however, migration of newborn cells into the granular layer of the hippocampus dentate gyrus was significantly reduced in prenatally deficient animals (P<0.01). We conclude that a prenatal VitC deficiency in guinea pigs leads to persistent impairment of postnatal hippocampal development which is not alleviated by postnatal repletion. Our findings place attention on a yet unrecognized consequence of marginal VitC deficiency during pregnancy.     

Food restriction induced thyroid changes and their reversal after refeeding in female rats and their pups

In the present study, two groups of pregnant female rats were submitted to food restriction (24 h fast versus 24 h diet intake) from the 14th day of pregnancy until either the 14th day (group B) or the 4th day after parturition (group C). All pups and their mothers were sacrificed on day 14 after delivery. The body weight of the 14-day-old pups (group B) was 46% less than the controls (group A). Free thyroxine and free triiodothyronine levels in the plasma were reduced by 44 and 16% in pups and by 20 and 36% in their mothers, respectively. These reductions were correlated with a decrease in thyroid iodine content of the pups (-50%) and their mothers (-24%). Radioiodine uptake (131I) by the thyroid gland of pups was significantly increased by 27%. Plasma TSH levels were decreased by 38% in pups and by 44% in dams. Morphological changes in thyroid glands were observed in energy restricted dams and in their pups. Some of follicles in pups were empty. Moroever in dams, we noted the presence of peripheral resorbed vacuoles, sign of thyroid hyperactivity. After a refeeding (group C) period of ten days, total recovery occurred in plasma thyroid hormone levels (FT4 and FT3) and in thyroid iodine contents of pups in spite of a partial recovery of body weights and plasma TSH levels. In dams, a partial recovery occurred in plasma thyroid hormone levels in spite of total recovery in thyroid iodine contents, while plasma TSH levels exceeded control values. A significant amelioration in thyroid histological aspects was observed in pups and their dams.     

Aluminum transfer through milk in female rats intoxicated by aluminum chloride

Female rats received an ip injection of aluminum chloride, (10 mg Al/kg/d) during the first 12 d after parturition; this treatment led to a reduction in food intake associated with a reduction in body wt. Pups of the intoxicated dams showed a growth retardation after postnatal day 7. One day after treatment, the female rats intoxicated with aluminum had a considerably higher level of aluminum in milk than controls. The aluminum levels of plasma, liver, spleen, and kidneys were also significantly higher in treated female rats than controls. On the contrary, in the same tissues of pups from treated or not treated dams, no differences in aluminum levels were observed. No effect of aluminum treatment was detected on plasma silicon levels in dams and pups.     

Zinc metabolism in lethal-milk mice. Otolith, lactation, and aging effects

Lethal-milk (lm), a recessive mutation, occurred in the C57BL/6J inbred strain of mice. Lactating lm dams produce a zinc-deficient milk that is lethal to all nursing pups. If foster-nursed on normal dams, lm pups survive and become reproductively mature. Injection of zinc-glycinate into the pups or zinc supplementation of the water of the lactating dams reduces lethality. Other pleiotropic effects in lm mice include congenital otolith defects with delayed righting, "tail-spinning," and abnormal swimming. These effects are diagnostic criteria for segregation of lm mice among backcross progeny. About 40 percent of the expected number of lm pups survive to weaning. Zinc supplementation of the dam improves development of saccular but not of utricular otoliths; zinc does not improve survival of the lm pups among backcross progenies. The lm mice over eight months of age also exhibit extensive hair loss, dermatitis, and skin lesions. Possible roles of metallothionein in zinc and copper metabolism are discussed in regard to the pleiotropic effects of the lethal-milk mutation.     

Prenatal ethanol exposure reduces the effects of excitatory amino acids in the rat hippocampus

Chronic alcohol ingestion during pregnancy can lead to the Fetal Alcohol Syndrome (FAS), a disorder marked by learning disabilities. A rat model of FAS was used by introducing pregnant Sprague-Dawley rats to a liquid diet containing 35% ethanol-derived calories (E), while a second group was pair-fed an isocaloric liquid diet without ethanol (P). A third group of pregnant dams received ad libitum lab chow (C). At parturition, pups from the E and P groups were cross-fostered by C mothers and all groups received lab chow. During adulthood, male offspring were sacrificed and hippocampal and prefrontal cortical slices were prelabeled with [3H] inositol. Phosphoinositide (PI) hydrolysis was determined by measuring the accumulation of [3H]inositol phosphates in the presence of LiCl in response to activation of various excitatory amino acid (EAA) receptors. In hippocampal slices, ibotenate- and quisqualate-induced PI hydrolysis was reduced in E compared to P and C animals. Moreover, the inhibitory effect of N-methyl-D-aspartate (NMDA) on carbachol-induced PI hydrolysis, evident in P and C animals, was completely abolished in the hippocampus of E animals. In contrast, in the prefrontal cerebral cortex, this inhibitory effect of NMDA prevailed even in the E animals. The evidence suggest that prenatal ethanol exposure alters the activity of EAA receptors in the hippocampal generation of 2nd messengers.     

Prenatal stress alters seizure thresholds and the development of kindled seizures in infant and adult rats

Stressful events during gestation and in the neonatal period have important effects on the later physical and mental health of the offspring. The present study tested the hypothesis that pre- and/or postnatal stress would affect seizure susceptibility in infant and adult rats, using the hippocampal kindling model. Prenatal stress consisted of daily restraint of the dam under bright light (for 45 min, 3 x / day) during either early gestation or mid/late gestation. Pups were compared to pups born to unstressed dams. Postnatal stress (administered on Days 4 and 5 after birth) consisted of either separation from the dam and placement in the bedding of a strange male for 1 h or injection of dexamethasone. Pups were compared to nonstressed siblings of the same litter. Both early and mid/late-gestation prenatal stress significantly lowered the after-discharge threshold (ADT) in infant, 14-day-old rat offspring, as compared to nonstressed control offspring. This effect on ADT was lost by adulthood. Mid/late-gestation stress increased the rate of kindled seizure development in infant rats and in their adult male, but not female, siblings. Postnatal stress had no significant effect on ADT or kindling rate. These findings indicate that prenatal stress, particularly during the latter half of pregnancy, may play an important role in increasing seizure vulnerability in the unborn offspring. These effects are more pronounced in infancy, but can also extend to adulthood.     

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.     

Enhancement of hippocampal mossy fiber activity in zinc deficiency and its influence on behavior

The extracellular concentration of glutamate in the hippocampus is increased by hippocampal perfusion with CaEDTA, a membrane-impermeable zinc chelator, suggesting that the activity of glutamatergic neurons in the hippocampus are influenced by the extracellular concentrations of zinc. In the present study, the relationship between the extracellular concentrations of zinc and mossy fiber activity in the hippocampus was examined in mice and rats fed a zinc-deficient diet for 4 weeks. Timm's stain, by which histochemically reactive zinc in the presynaptic vesicles is detected, was attenuated in the hippocampus in zinc deficiency. The extracellular signal of ZnAF-2, a membrane-impermeable zinc indicator, was also lower in the hippocampal CA3, suggesting that the basal extracellular concentrations of zinc are lower maintained in zinc deficiency. To check mossy fiber activity after 4-week zinc deprivation, the decrease in the signal of FM4-64, an indicator of presynaptic activity (exocytosis), at mossy fiber synapses was measured under the condition of spontaneous depolarization. The decrease was significantly facilitated by zinc deficiency, suggesting that the basal exocytosis at mossy fiber synapses is enhanced by zinc deficiency. On the other hand, the increase in anxiety-like behavior was observed in the open-field test after 4-week zinc deprivation. The present study demonstrates that the decrease in the basal extracellular concentrations of zinc may be linked to the enhancement of the basal mossy fiber activity in zinc deficiency. This decrease seems to be also involved in neuropsychological behavior in zinc deficiency.     

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…