Long lasting effects of intrauterine growth retardation on basal and 5-HT-stimulated Na+/K+-ATPase in the brain of developing rats

Intrauterine growth retardation induced by ligation of the uterine vessels in pregnant rats on the 5th day before delivery was associated with brain and body weights of hypotrophic offspring significantly lower than those of pair-aged control rats, even after 6 weeks of postnatal rearing under normal conditions. In vitro measurements in homogenates indicated that Na⁺/K⁺-ATPase in the forebrain, cerebellum and hippocampus was less active in hypotrophic rats than in pair-aged controls for at least the first month after birth. However, 5-HT and related agonists (RU-24969, bufotenine, and to a lower extent, tryptamine) stimulated Na⁺/K⁺-ATPase activity more efficiently in tissues from hypotrophic rats than in those from control animals. Opposite changes were noted in the brain stem: basal Na⁺/K⁺-ATPase activity was higher in hypotrophic rats during the second half of the first postnatal month but the stimulatory effect of 5-HT was lower than in pair-aged control animals. Since potent 5-HT antagonists such as cinanserin, methiothepin and methysergide, prevented the 5-HT induced-activation of Na⁺/K⁺-ATPase in brain homogenates, these results are discussed in relation with the possible existence of a specific 5-HT receptor controlling Na⁺/K⁺-ATPase activity in the rat brain.     

Effect of hyperphenylalaninemia induced during suckling on brain DNA metabolism in rat pups

We studied DNA metabolism (synthesis and degradation) in brain to investigate the effect of hyperphenylalaninemia induced in rats by treatment with PCPA or MPA plus PHE during suckling (4th–20th days of postnatal age) on cell proliferation and naturally occurring cell death. The incorporation of¹⁴C in DNA as percent of total radioactivity in the tissue, 30 min after administration of [¹⁴C]thymidine served as a measure of DNA synthesis in vivo, and the amount of radioactivity recovered in DNA as percent of total¹⁴C in the tissues of 21 day old rats, injected with [¹⁴C]thymidine on 2nd day after birth, indicated the turnover (degradation) of DNA. The results showed that the DNA content of cerebellum as well as cerebrum was reduced by treatment with PCPA plus PHE, while treatment with MPA plus PHE had no effect on DNA content in cerebellum but reduced the levels in cerebrum. Treatment with PCPA or MPA plus PHE reduced the synthesis of DNA in cerebrum of 11 day old rats but not in 21 day old rats, and the treatments did not affect DNA synthesis in cerebellum of either 11 or 21 day old rats. The turnover (degradation) of DNA was increased in both cerebellum and cerebrum from rats treated with PCPA plus PHE but MPA plus PHE treatment did not alter the DNA turnover either in cerebellu or in cerebrum. The activity of acid DNase was reduced in both cerebellum and cerebrum from 11 as well as 21 day old rats treated with PCPA plus PHE, but the enzyme activity was not altered in the tissues from rats of both ages treated with MPA plus PHE. The data thus indicate that in rats treated with PCPA plus PHE the reduction in cerebral DNA levels occurs due to reduced synthesis and/or increased turnover (degradation) of DNA but that the reduction in cerebellar DNA may occur only as a result of increased turnover (degradation), and that in rats treated with MPA plus PHE the reduction in cerebral DNA must occur due to reduced synthesis. This suggests that treatment of rats with PCPA plus PHE during suckling inhibits cell proliferation and/or increases naturally occurring cell death in both cerebellum and cerebrum while treatment with MPA plus PHE inhibits only cell proliferation and in cerebrum alone.     

Preventive Effect of CuCl2 on Behavioral Alterations and Mercury Accumulation in Central Nervous System Induced by HgCl2 in Newborn Rats

This study investigated the benefits of Cu preexposition on Hg effects on behavioral tests, acetylcholinesterase (AChE) activity and Hg, and essential metal contents in the cerebrum and cerebellum of neonate rats. Wistar rats received (subcutaneous) saline or CuCl₂·2H₂O (6.9 mg/kg/day) when they were 3 to 7 days old and saline or HgCl₂ (5.0 mg/kg/day) when they were 8 to 12 days old. Mercury exposure reduced the performance of rats in the negative geotaxis (3–13 days) and beaker test (17–20 days), inhibited cerebellum AChE activity (13 days), increased cerebrum and cerebellum Hg (13 days), cerebrum Cu (13 days), and cerebrum and cerebellum Zn levels (33 days). The performance of rats in the tail immersion and rotarod tests as well as Fe and Mg levels were not altered by treatments. Copper prevented all alterations induced by mercury. These results are important to open a new perspective of prevention and/or therapy for mercury exposure.     

Oxygen-sensitivity of potassium fluxes across plasma membrane of cerebellar granule cells

This study focuses on the oxygen-dependence of active and passive K⁺ fluxes across membranes of cerebellar granule cells of neonatal rats. Maximal Na⁺,K⁺-ATPase activity along with minimal passive K⁺ influx was observed within oxygen concentration range characteristic for neonatal rat cerebellum. Prolonged exposure to hypoxia as well as hyperoxia resulted in suppression of the Na⁺,K⁺-ATPase and activation of the passive K⁺ flux. Toxic effects of hypoxia could be partially prevented by inhibition of NO production with L-NAME. This was accomplished by suppression of Na⁺,K⁺-ATPase with subsequent reduction in ATP consumption concurrently with the reduction in passive K⁺ flux. Activation of the Na⁺,K⁺-ATPase by NO at physiological pO₂ could be abolished by inhibition of NO synthase by L-NAME or soluble guanylyl cyclase with ODQ. However, treatment of cells with activator of PKG Rp-8-CTP did not mimic normoxic activation of the active K⁺ influx. Oxygen-induced responses under normoxic conditions were differentially mediated by α1 isoform of the Na⁺,K⁺-ATPase catalytic subunit, whereas α2/3 isoform was predominantly active under conditions of severe hypoxia. We conclude that both hypoxia and hyperoxia trigger a gradual dissipation of transmembrane K⁺ gradient and loss of excitability of cerebellar neurons. The latter may be partially reversed by suppression of NO production under hypoxic conditions     

26Al incorporation into the brain of suckling rats through maternal milk

Aluminium inhibits prenatal and postnatal brain development. However, aluminium incorporation into the brain of sucklings through maternal milk has not yet been well clarified because aluminium lacks a suitable isotope for radioactive tracer experiments. Using 26Al (26AlCl(3)) as a tracer, we measured 26Al incorporation into the brain of suckling rats by accelerator mass spectrometry. Lactating rats were subcutaneously injected with 26AlCl(3) from day 1 to day 20 postpartum. Suckling rats were weaned from day 21 postpartum. From day 5 to day 20 postpartum, the amounts of 26Al measured in the cerebrum, cerebellum, spinal cord, liver, and kidneys of suckling rats increased significantly. After weaning, the amounts of 26Al in the liver and kidneys decreased remarkably. Alternatively, in the cerebrum, cerebellum, and spinal cord, as much as 12 to 20% of the 26Al amounts present on day 20 postpartum remained in the tissues on day 730 postpartum. As the life span of rats is about 2 years, we conclude that considerable amounts of the 26Al taken up into the brain of suckling rats through maternal milk remained in their brain throughout their lifetime.     

Testicular Morphology and Cell Proliferation Kinetics of Immature Germ Cells and Sertoli Cells In Suckling Undernourished Rats

Undernutrition during suckling was induced in newborn rats by increasing the litter size to sixteen pups to be fed by one mother. Animals reared in litters of eight served as controls. Undernourished animals showed retarded body and testicular growth during a suckling period of 22 days. Sequential morphogenesis of the testis was not altered up to 15 days of age. However, certain morphological alterations in Sertoli cells and Leydig cells were observed from 15 days onwards. Cell generation cycle of spermatogonial germ cells and supporting cells (future Sertoli cells) on day 9 showed marked prolongation of DNA synthetic phase (S), unaltered post-DNA synthetic phase (G₂) and total cycle (T_c) and shortening of the pre-DNA synthetic phase (G₁) indicating a depression in DNA synthesis in undernutrition.     

Regulation of Glial Na+/K+-ATPase by Serotonin: Identification of Participating Receptors

The purpose of the present study was the characterization of the receptors participating in the regulatory mechanism of glial Na⁺/K⁺-ATPase by serotonin (5-HT) in rat brain. The activity of the Na⁺ pump was measured in four brain regions after incubation with various concentrations of serotoninergic agonists or antagonists. A concentration-dependent increase in enzyme activity was observed with the 5-HT_1A agonist R (+)-2-dipropylamino-8-hydroxy-1,2,3, 4-tetrahydronaphthalene hydrobromide (8-OH-DPAT) in homogenates or in glial membrane enriched fractions from cerebral cortex and in hippocampus. Spiperone, a 5-HT_1A antagonist, completely inhibited the response to 8-OH-DPAT but had no effect on Na⁺/K⁺-ATPase activity in cerebellum where LSD, a 5-HT₆ agonist, elicited a dose-dependent response similar to that of 5-HT. In brainstem, a lack of reponse to 5-HT and other agonists was confirmed. Altogether, these results show that serotonin modulates glial Na⁺/K⁺-ATPase activity in the brain, apparently not through only one type of 5-HT receptor. It seems that the receptor system involved is different according to the brain region. In cerebral cortex, the response seems to be mediated by 5-HT_1A as well as in hippocampus but not in cerebellum where 5-HT₆ appears as the receptor system involved.     

Effects of sub-chronic aluminum chloride exposure on rat ovaries

Aims

This experiment investigated the effects of sub-chronic aluminum chloride (AlCl₃) exposure on rat ovaries.

Main methods

Eighty female Wistar (5 weeks old) rats, weighed 110–120 g, were randomly divided into four treatment groups: control group (CG), low-dose group (LG, 64 mg/kg BW AlCl₃), mid-dose group (MG, 128 mg/kg BW AlCl₃) and high-dose group (HG, 256 mg/kg BW AlCl₃). The AlCl₃ was administered in drinking water for 120 days. The ovarian ultrastructure was observed. The activities of acid phosphatase (ACP), alkaline phosphatase (ALP), succinate dehydrogenase (SDH), Na⁺–K⁺-ATPase, Mg^2 +-ATPase and Ca^2 +-ATPase, the contents of Fe, Cu and Zn, and the protein expression of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) in the ovary were determined.

Key findings

The results showed that the structure of the ovary was disrupted, the activities of ALP, ACP, SDH, Na⁺–K⁺-ATPase, Mg^2 +-ATPase and Ca^2 +-ATPase, the contents of Zn, Fe and the protein expression of FSHR and LHR were lowered, and the content of Cu was increased in AlCl₃-treated rats than those in control.

Significance

The results indicate that sub-chronic AlCl₃ exposure caused the damage of the ovarian structure, the disturbed metabolism of Fe, Zn and Cu and the decreased activities of Na⁺–K⁺-ATPase, Mg^2 +-ATPase and Ca^2 +-ATPase in the ovary, which could result in suppressed energy supply in the ovary. A combination of suppression of energy supply and reduction of expression of FSHR and LHR could inhibit ovulation and corpus luteum development, leading to infertility in female rats.     

(Na,K)-ATPase activity of embryonic chick heart and skeletal muscles as a function of age

The specific activity of the membrane (Na⁺,K⁺)-ATPase of intact chick embryonic hearts (ventricles) was measured as a function of embryonic age. The membranes were prepared by a NaI extraction method of the 100 000 × g fraction which selectively removes much of the ouabain-insensitive Mg²⁺-ATPase. The specific activity of the myocardial (Na⁺, K⁺)-ATPase increased markedly during embryonic development from mean levels of about 3.0 μmoles P_i per h per mg protein at day 6 to 7.4 at day 16 and 11.0 at day 20 (1 day prior to hatching); the adult level was about the same as that of the 16-day-old chick. The relative activities with respect to that at day 16 (from paired experiments) averaged 43 % (day 6), 56 % (day 9), 73 % (day 13), 140 % (day 20), 115 % (day 23), 126 % (day 30) and 96 % (adult). There was a similar increase in relative activity of the (Na⁺,K⁺)-ATPase from chick skeletal (leg) muscles during development. If the total protein content per unit membrane area and the turnover number remain constant, the data indicate that the surface density of the (Na⁺,K⁺)-ATPase molecules increases during embryonic development; thus, the cation pumping capabilities of the cells should be enhanced if the surface area/volum ratio of the myocardial cells remains unchanged. However, the pumping capabilities of the very young cells must be sufficient to maintain the known high [K⁺]_i and low [Na⁺]_i already present; their internal activities actually change only to a small extent during development. Since there is a known increase in K⁺ permeability during embryonic development, thereby increasing the demand on the cation pump, the observed increase in activity of the (Na⁺,K⁺)-ATPase tends to compensate for this.     

Subcellular distribution of carbonic anhydrase and Na+,K+-ATPase in the brain of the hyt/hyt hypothyroid mice

Activities of carbonic anhydrase and Na⁺,K⁺-ATPase in tissue homogenates and in subcellular fractions from different brain regions were studied in inherited primary hypothyroid (hyt/hyt) mice. The body weight, the weight of different brain regions, and the plasma thyroxine and triiodothyronine levels of hyt/hyt mice were significantly lower than those of the age-matched hyt/+ controls. In tissue homogenates of cerebral cortex, brain stem and cerebellum of hypothyroid mice, the activity of carbonic anhydrase (units/mg protein) was 59.2, 57.6, and 43.2%, and the activity of Na⁺,K⁺-ATPase (nmol Pi/mg protein/min) was 73.7, 74.4 and 68.7%, respectively, of that in corresponding regions of euthyroid littermates. The decrease in enzyme activity in tissue homogenates was also reflected in different subcellular fractions. In cerebral cortex and brain stem, carbonic anhydrase activity in cytosol, myelin and mitochondrial fractions of hypothyroid mice was about 45–50% of that in euthyroid mice, while in cerebellum the carbonic anhydrase activity in these subcellular fractions of hyt/hyt mice was only 33–38% of that in hyt/+ controls. Na⁺,K⁺-ATPase activity in myelin fraction of different brain regions of hyt/hyt mice was about 34–42% of that in hyt/+ mice, while in mitochondria, synaptosome and microsome fractions were about 44–52, 46–53, and 66–68%, respectively of controls. These data indicate that the activity of both carbonic anhydrase and Na⁺,K⁺-ATPase was affected more in the myelin than other subcellular fractions and more in the cerebellum than cerebral cortex and brain stem by deficiency of thyroid hormones. A reduction in the activity of transport enzymes in brain tissues as a result of thyroid hormone deficiency during the critical period of development may underlie permanent nervous disorders in primary hypothyroidism.     

Changes of sodium and ATP affinities of the cardiac (Na,K)-ATase during and after nitric oxide deficient hypertension

In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na⁺, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N^G-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in K_m and V_max values were observed in NO-deficient rats. During activation with Na⁺, the V_max remained unchanged, however the K_Na increased by 50%, indicating a profound decrease in the affinity of the Na⁺-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered K_m value for ATP. The K_Na value for Na⁺ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na⁺-extrusion from cardiac cells as a consequence of deteriorated Na⁺-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na⁺ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity. (Mol Cell Biochem 000: 000-000, 1999)     

Role of Na+/K+-stimulated adenosine triphosphatase in the action of dopaminergic-D2 receptors of the liver in rats

The dopamine receptor agonist, bromocriptine, in a dose of 10 mg/kg i.p. for 14 days, in rats caused a significant increase in liver Na⁺/K⁺-ATPase activity, whereas sulpiride, a dopamine receptor antagonist, in a dose of 10 mg/kg, i.p. for 14 days, in rats, caused a significant decrease in liver Na⁺/K⁺-ATPase activity. Injection of bromocriptine and sulpiride simultaneously in a group of rats, under the same conditions and using the same doses caused a complete block of both stimulatory activity of bromocriptine and inhibitory activity of sulpiride on liver Na⁺/K⁺-ATPase activity. It is suggested that Na⁺/K⁺-ATPase may have a role in the action of dopaminergic-D₂ receptors.     

The effect of dietary selenium supplementation on cadmium absorption and retention in suckling rats

Selenium (Se) reduces cadmium (Cd) toxicity in adult animals, but its effects in newborn animals are still unknown. This study investigated Cd (as CdCl₂) absorption, distribution, and retention in suckling rats receiving oral Se supplementation (as Na₂SeO₃) in equimolar doses (8 μmol Cd and/or Se per kg b.w./day). Selenium was given either before and during Cd exposure (Se_pre + Cd group; pre-treatment group) or only during Cd exposure (Se + Cd group). Rats were treated from postnatal day (PND) 6–14 as follows: controls (H₂O, PND 6–14), Se (PND 10–14), Cd (PND 10–14), Se_pre + Cd (Se PND 6–14 + Cd PND 10–14) and Se + Cd (Se + Cd PND 10–14). Selenium supplementation, especially pre-treatment, decreased Cd levels in the blood, brain, liver and kidney of suckling rats. Selenium levels in plasma, brain, and kidney also decreased. These findings suggest that higher Se intake could efficiently reduce Cd retention during the suckling period.     

EFFECT OF UNDERNUTRITION ON CELL FORMATION IN THE RAT BRAIN

Abstract— Rats were undernourished by approximately halving the normal food given from the 6th day of gestation throughout lactation. Growth of the foetuses was nearly normal, in marked contrast to the severe retardation caused by undernutrition during the suckling period. In comparison with controls the size and the DNA content of the brain were permanently reduced by undernutrition during the suckling period: this effect was relatively small, approx. 15 per cent decrease at 21 and 35 days. The rate of ¹⁴C incorporation into brain DNA at 30 min after administration of [2-¹⁴C] thymidine was taken as an index of mitotic activity; compared with controls there was severe reduction in mitotic activity (maximal decrease by about 80 per cent at 6 days in the cerebrum and by 70 per cent at 10 days in the cerebellum). The rate of acquisition of cells was calculated from the slopes of the logistic curves fitted to the estimated DNA contents. In normal animals the maximal slope was attained at 2·7 days and at 12·8 days after birth in cerebrum and cerebellum respectively; the daily acquisition of cells at these times was 4·8 × 10⁶ and 18 × 10⁶ cells respectively. The fractional increase in cell number at the maximum was 5·4 percent per day in the cerebrum and 15·2 per cent per day in the cerebellum. The rate of acquisition of cells relative to the rate of mitotic activity was higher in the brains of undernourished animals than in controls. One of the compensatory mechanisms for the severe depression of mitotic activity in the brain of undernourished animals Seems to involve a reduction in the normal rate of cell loss.     

Contextual Fear Conditioning in Maternal Separated Rats: The Amygdala as a Site for Alterations

The first 2 weeks of life are a critical period for neural development in rats. Repeated long-term separation from the dam is considered to be one of the most potent stressors to which rat pups can be exposed, and permanently modifies neurobiological and behavioral parameters. Prolonged periods of maternal separation (MS) usually increase stress reactivity during adulthood, and enhance anxiety-like behavior. The aim of this study was to verify the effects of maternal separation during the neonatal period on memory as well as on biochemical parameters (Na⁺, K⁺-ATPase and antioxidant enzymes activities) in the amygdala of adult rats. Females and male Wistar rats were subjected to repeated maternal separation (incubator at 32 °C, 3 h/day) during postnatal days 1–10. At 60 days of age, the subjects were exposed to a Contextual fear conditioning task. One week after the behavioral task, animals were sacrificed and the amygdala was dissected for evaluation of Na⁺, K⁺-ATPase and antioxidant enzymes activities. Student-t test showed significant MS effect, causing an increase of freezing time in the three exposures to the aversive context in both sexes. Considering biochemical parameters Student-t test showed significant MS effect causing an increase of Na⁺, K⁺-ATPase activity in both sexes. On the other hand, no differences were found among the groups on the antioxidant enzymes activities [superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT)] in male rats, but in females, we found a significant MS effect, causing an increase of CAT activity and no differences were found among the groups on SOD and GPx activities. Our results suggest a role of early rearing environment in programming fear learning and memory in adulthood. An early stress experience such as maternal separation may increase activity in the amygdala (as pointed by the increased activity of Na⁺, K⁺-ATPase), affecting behaviors related to fear in adulthood, and this effect could be task-specific.     

REGIONAL DISTRIBUTION OF GLUTAMIC ACID DECARBOXYLASE IN THE DEVELOPING BRAIN OF THE PYRIDOXINE-DEFICIENT RAT

—Glutamic acid decarboxylase was determined in seven brain regions: hypo-thalamus; midbrain; thalamus; corpus striatum; cerebral cortex-hippocampus; medulla-pons; and cerebellum, of suckling rats subjected to Vitamin B₆ deficiency for 2 weeks from birth; of adult rats subjected to the deficiency for 5 weeks and of their respective controls. Large regional variations in the enzyme activity were found in brains of both adult and suckling control rats. The activity of the enzyme (assayed without pyridoxal phosphate) and its saturation with endogenous cofactor were markedly reduced in all brain regions of both suckling and adult pyridoxine-deficient rats. The apoenzyme (activity assayed with pyridoxal phosphate), in adult rat brain, showed no change with the deficiency in all regions except in the cerebellum where it increased slightly. In pyridoxine-deficient suckling rat brain, the apoenzyme increased substantially in all regions suggesting a process of enzyme induction. The increase in apoenzyme varied from region to region.     

Oxidative stress induced by gibberellic acid on kidney tissue of female rats and their progeny: biochemical and histopathological studies

Gibberellic acid (GA₃) is an endogenous plant growth regulator used worldwide in agriculture. The objective of this study was to investigate the effects of GA₃ on the kidney function of adult rats and their pups. Female Wistar rats were given daily 200 ppm GA₃ in drinking water from the 14th day of pregnancy until day 14 after delivery. GA₃ induced nephrotoxicity, as evidenced by a reduction in the 24-h urine volume and an increase in plasma creatinine, urea and uric acid levels. Nephrotoxicity was objectified by a significant increase of malondialdehyde level and a decrease of antioxidant enzyme activities like catalase, superoxide dismutase, glutathione peroxidase and glutathione content in kidneys of suckling pups and their mothers. Kidney histological studies confirmed biochemical parameters. We concluded that the exposure of rats to GA₃ induced oxidative stress and histopathological changes in kidneys of suckling rats and their mothers during late pregnancy and early postnatal periods.     

Modification by hypoxia and drug treatment of cerebral ATPase plasticity

The plasticity of synaptosomal non-mitochondrial ATPases was evaluated in cerebral cortex from 3-month-old normoxic rats and rats subjected to either mild or severe intermittent normobaric hypoxia [12 hr daily exposure to N₂O₂ (9010 or 91.58.5) for four weeks]. The activities of Na⁺, K⁺-ATPase, low- and high-affinity Ca²⁺-ATPase, Mg²⁺-ATPase, and Ca²⁺, Mg²⁺-ATPase were assayed in synaptosomes and synaptosomal subfractions, namely synaptosomal plasma membranes and synaptic vesicles. The evaluations were performed after a 4-week treatment with saline (controls) or -adrenergic agents (-yohimbine, clonidine), a vasodilator compound (papaverine), and an oxygen-partial pressure increasing agent (almitrine). These treatments differently changed the adaptation to chronic intermittent hypoxia characterized by a decrease in the activity of Na⁺, K⁺-ATPase, Ca²⁺,Mg²⁺-ATPase, and high-affinity Ca²⁺-ATPase, concomitant with a modification in the activity of Mg²⁺-ATPase supported in a different way by the enzymatic forms located into the synaptosomal plasma membranes and synaptic vesicles.     

Maternal Hypermethioninemia Affects Neurons Number,Neurotrophins Levels,Energy Metabolism,and Na<Superscript>+</Superscript>,K<Superscript>+</Superscript>-ATPase Expression/Content in Brain of Rat Offspring

In the current study, we verified the effects of maternal hypermethioninemia on the number of neurons, apoptosis, nerve growth factor, and brain-derived neurotrophic factor levels, energy metabolism parameters (succinate dehydrogenase, complex II, and cytochrome c oxidase), expression and immunocontent of Na⁺,K⁺-ATPase, edema formation, inflammatory markers (tumor necrosis factor-alpha and interleukin-6), and mitochondrial hydrogen peroxide levels in the encephalon from the offspring. Pregnant Wistar rats were divided into two groups: the first one received saline (control) and the second group received 2.68 μmol methionine/g body weight by subcutaneous injections twice a day during gestation (approximately 21 days). After parturition, pups were killed at the 21st day of life for removal of encephalon. Neuronal staining (anti-NeuN) revealed a reduction in number of neurons, which was associated to decreased nerve growth factor and brain-derived neurotrophic factor levels. Maternal hypermethioninemia also reduced succinate dehydrogenase and complex II activities and increased expression and immunocontent of Na⁺,K⁺-ATPase alpha subunits. These results indicate that maternal hypermethioninemia may be a predisposing factor for damage to the brain during the intrauterine life.