Effects of maternal cadmium administration on development of monoaminergic, GABAergic and glutamatergic systems.

The effects of maternal exposure to 10mgCd/l (as cadmium acetate) in drinking water during gestation and lactation on the development of monoaminergic and aminoacidergic systems were studied in discrete brain areas of the pups: striatum, cerebral cortex, dorsal hippocampus and basal-medial hypothalamus. Hippocampal levels of serotonin and 5-hydroxyindolacetic acid were significantly reduced in rats exposed to Cd whereas the dopamine content was not significantly affected by Cd. Glutamate concentration decreased in hypothalamus and increased in hippocampus, while gamma-aminobutiric acid content decreased only in cerebral cortex.

Influence of metyrapone treatment during pregnancy on the development and maturation of brain monoaminergic systems in the rat.

Aim: This study examines the effect of reducing the corticosterone levels of gestating rat dams on the postnatal development and maturation of monoaminergic systems in their offspring's brains.

Methods: Metyrapone, an inhibitor of CORT synthesis, was administered to pregnant rats from E0 to E17 of gestation. Monoamine concentrations were determined in male and female offspring at postnatal days (PN) 23 and 90 in the hippocampus, hypothalamus and striatum.

Role of maternal corticosterone in the development and maturation of the aminoacidergic systems of the rat brain.

Previous studies have suggested an important role for maternal glucocorticoids in the development of the aminoacidergic systems of the rat brain. This study examines the effect of metyrapone (2-methyl-1,2-di-3-pyridyl-1-propanone), i.p.

Effect of intrauterine position on sex differences in the gabaergic system and behavior of rats.

In multiparous species such as the rat (in this case the albino Wistar strain), steroid influence during fetal growth is affected by the relative intrauterine position of male and female fetuses and is stronger when the potential effects of contiguity and caudal position are combined. The effect of intrauterine position on gonadal steroid levels in neonatal and adult animals was examined using radioimmunoassay techniques. Since the organizing effect of prenatal steroids may influence the postnatal GABA content, HPLC was used to determine the gabaergic content in several hypothalamic and limbic areas in the adult rat.

Effect of 17-beta-estradiol on dopamine, serotonine and GABA striatal levels in 6-hydroxydopamine-treated rats.

Intrastriatal injection (16microg) of the neurotoxic dopaminergic agent 6-hydroxydopamine (6-OHDA) in ovariectomized rats caused important reductions in striatal dopamine (DA) and serotonin (5-HT) levels and an increase in GABA content. Treatment of ovariectomized rats with estradiol (5 mg 17-beta-estradiol administered by a subcutaneous cannula) before 6-OHDA injection maintained the control levels of these neurotransmitters. The administration of estradiol after 6-OHDA injection did not lead to their recovery.

Effects of maternal adrenalectomy on the developing dopaminergic system.

The present study show that maternal adrenalectomy affect the developmental model of the dopaminergic system in the hypothalamus and hippocampus, with sexual dimorphism observed in both areas. No changes were observed in the developmental dopamine (DA) model of the cortex and striatum through dopamine levels were increased in striatum.

Role of maternal adrenal glands on the developing serotoninergic and aminoacidergic systems of the postnatal rat brain.

Serotonin, gamma-aminobutyric acid and glutamate, which are regulated by glucocorticoids in the central nervous system, are involved in neuroendocrine functions and the development of the brain. The present study investigates the effect of maternal adrenalectomy on the developing serotoninergic, GABAergic and glutamatergic systems. Neurotransmitter levels were measured in four brain areas of both male and female offspring on postnatal days 1, 8, 12 and 22.

Maternal adrenalectomy affects development of adrenal medulla.

This work investigates the effects of maternal adrenalectomy (ADX) on the development of the adrenal medulla. Adrenal catecholamines (AC) were measured at postnatal day (PN) 1, 8, 12 and 22 in rat offspring of ADX dams and in pups of control dams. The pups of ADX rats showed a reduction in AC concentrations in the adrenal medulla at PN 1, 12 and 22, although these were higher than in the pups of sham dams at PN 8.

Study of the activity of several brain enzymes like markers of the neurotoxicity induced by perinatal exposure to lead and/or cadmium.

Five enzymes, considered keys to the correct function of the central nervous system (CNS) were chosen to study their utility as markers of the possible neurotoxic effects produced by the perinatal exposure to lead and/or cadmium. With this aim, lead acetate (300 mg/l) and/or cadmium acetate (10 mg/l) were administered to pregnant Wistar rats from day 1 of pregnancy to parturition (day 0) or until weaning (day 21). Brains were used to determine the activity of acid phosphatase (ACP), alkaline phosphatase (ALP), catalase (CAT), acetylcholinesterase (AchE) and ATP-ases (Na(+)/K(+) and Mg(2+)/Ca(2+) dependent).

Study of the neurochemical alterations produced in discrete brain areas by perinatal low-level lead exposure.

Although the neurotoxic effects of Pb are well documented, the subcellular mechanisms of this action in the central nervous system are not fully understood. The present work examines some neurochemical parameters in discrete brain areas of pups whose mothers were intoxicated via drinking water with lead (300 mg/L), from day 1 of pregnancy until postnatal day 12. Lead intoxication produced a significant reduction in the activity of the enzymes alkaline phosphatase and ATP-ase in the brain.

Perinatal exposure to lead and cadmium affects anxiety-like behaviour.

The present study examines the effects of early simultaneous exposure to low level of lead and cadmium on anxiety-like behaviour in the rat, and on monoamine levels in the hypothalamus and hippocampus at weaning and adult animals. Rats were intoxicated with cadmium acetate (10 mg/l) and lead acetate (300 mg/l) in drinking water from the beginning of pregnancy until weaning. Maternal co-exposure to lead and cadmium produced mainly alterations in dopaminergic and serotoninergic systems of hippocampus in both age studied, while noradrenaline content in hypothalamus and hippocampus remained unchanged at 75 days of age.

Effects of maternal lead administration on monoaminergic, GABAergic and glutamatergic systems.

The effects of perinatal exposure to lead (300 mg/l) on the development of monoaminergic and aminoacidergic systems were evaluated in the striatum, cerebral cortex (Cx), dorsal hippocampus (d-Hipp) and basal-medial hypothalamus. Maternal exposure to lead produced regional alterations in monoamine content, with increases in dopamine and serotonin or their metabolites. Further, decreased glutamate levels were seen in all brain regions studied, while GABA content decreased only in the Cx.

Pb and Cd poisoning during development alters cerebellar and striatal function in rats.

The present study was designed to examine more fully the neurochemical and behavioral interactions that derive from continued lead and cadmium poisoning in pups, whose mothers were exposed via drinking water (300 mg/l of Pb and 10 mg/l of Cd) throughout pregnancy and lactation. At weaning, these metals produced an increase in DOPAC, 5-HT and 5-HIAA contents in cerebellum, but the monoamine contents in striatum remained unaltered. The cerebral energetic metabolism was modified by the Cd-Pb exposition only in striatum.

Deprenyl protects from MPTP-induced Parkinson-like syndrome and glutathione oxidation in rat striatum.

An intrastriatal injection with 18.8 nmoles of the neurotoxic agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced in rats a progressive parkinsonism characterized by a major loss of striatum dopamine (DA) levels and an increased turnover of this neurotransmitter 96 h after the administration. In addition, the intrastriatal administration of MPTP produced an alteration in various behavioral markers of motor activity.

The effects of acute treatment with delta9-THC on exploratory behaviour and memory in the rat.

The aim of the present study was to evaluate the effects of delta9-tetrahydrocannabinol (delta9-THC) on exploratory behaviour and memory, independent of its locomotor suppressive effects. Dopamine (DA) and noradrenaline (NA) contents were determined in the areas of the brain directly related to such behaviours (hippocampus, striatum and amygdala). An acute dose of delta9-THC led to a decrease in exploratory parameters and motor activity during the holeboard test.

Effect of MPTP on brain mitochondrial H2O2 and ATP production and on dopamine and DOPAC in the striatum.

An experimental rat model of Parkinson's disease was established by injecting rats directly in the striatum with the neurotoxic agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In order to study the action mechanism of this neurotoxic agent, MPTP and its main metabolite 1-methyl-4-phenylpyridinium (MPP+) were also added to suspensions of pyruvate/malate-supplemented nonsynaptic brain mitochondria, and the rates of hydrogen peroxide and ATP production were measured. Intrastriatal administration of MPTP produced a pronounced decrease in striatal dopamine levels (p < 0.

Neurochemical changes in newborn rat's brain after gestational cadmium and lead exposure.

Gestational administration of cadmium (10 mg/l) and lead (300 mg/l) produced a strong decrease in proteins at birth (-17%) and on day 5 (-31%) as well as in brain lipid amount on both days (-11 and -23%, respectively). At day 5 postnatal the exposure also produced a marked decrease in DNA and RNA concentrations with respect to the control group. On the other hand, we found a significant increase of indoleamine content in all brain areas studied in the cadmium-lead group and so the dopamine and its metabolite in mesencephalon, whereas dopamine levels in metencephalon decreased significantly.

The chemically inducible plant cytochrome P450 CYP76B1 actively metabolizes phenylureas and other xenobiotics.

Cytochrome P450s (P450s) constitute one of the major classes of enzymes that are responsible for detoxification of exogenous molecules both in animals and plants. On the basis of its inducibility by exogenous chemicals, we recently isolated a new plant P450, CYP76B1, from Jerusalem artichoke (Helianthus tuberosus) and showed that it was capable of dealkylating a model xenobiotic compound, 7-ethoxycoumarin. In the present paper we show that CYP76B1 is more strongly induced by foreign compounds than other P450s isolated from the same plant, and metabolizes with high efficiency a wide range of xenobiotics, including alkoxycoumarins, alkoxyresorufins, and several herbicides of the class of phenylureas.

Molecular cloning and functional expression in yeast of CYP76B1, a xenobiotic-inducible 7-ethoxycoumarin O-de-ethylase from Helianthus tuberosus.

In order to obtain plant markers of chemical stress and possible tools for the bio-monitoring of pollution, a protein purification/PCR approach was used to isolate cDNAs of xenobiotic-inducible P450 oxygenases. O-dealkylation of 7-ethoxycoumarin is catalysed in Helianthus tuberosus by cytochromes P450 strongly inducible by a wide range of xenobiotics. Therefore, a 7-ethoxycoumarin O-de-ethylase (ECOD) was purified from induced tuber tissues (Batard et al.

Effect of metyrapone administration in pregnant rats on monoamine concentration in fetal brain.

Studies performed in our laboratory indicate that the adrenal deprivation during gestation can greatly influence the fetal catecholamines development in several cerebral areas. The present study was undertaken to determine whether the administration of metyrapone to pregnant rats affects the content of monoamines in fetal brain at term. To test wether the content of monoamines in fetal brain is regulated, at least in part, by endogenous glucocorticoids, pregnant rats were injected for 5 days prior to delivery with metyrapone, an adrenal 11-beta-steroid hidroxylase inhibitor which crosses the placenta and blocks endogenous glucocorticoid synthesis, or saline.

Gestational administration of cadmium alters the neurotransmitter levels in newborn rat brains.

The effects of gestational and early lactational intoxication by cadmium (Cd) were studied in the brain of young Wistar rats. Pregnant rats were exposed to 10 mg of cadmium acetate per litre of drinking water, from initiation of pregnancy to parturition or until postnatal day 5. At birth or on postnatal day (PND) 5 the pups were weighed, sacrificed and brains were removed and frozen for later study.

Maternal exposure to delta 9-tetrahydrocannabinol (delta 9-THC) alters indolamine levels and turnover in adult male and female rat brain regions.

Perinatal exposure to delta 9-THC has been shown to produce effects on brain development. In this study we evaluated the changes induced by maternal exposure to delta 9-THC (5 mg/kg per day) from gestational day 5 to postnatal day 24 in eight discrete brain areas on the central serotoninergic system in both adult male and female rats. These result show that maternal exposure to delta 9-THC from gestational day 5 to postnatal day 24 affects development of the various central indoleaminergic system of the offsprings brain.

Effect of maternal delta 9-tetrahydrocannabinol on developing serotonergic system.

In this study we investigated the effects of maternal delta 9-tetrahydrocannabinol on the developing serotonergic system. A daily dose of delta 9-tetrahydrocannabinol (5 mg/kg body weight) was administered p.o.

Neurotoxic effects of gestational administration of low-dose lead acetate.

Lead acetate (300 mg l-1) was administered to pregnant Wister rats from day 1 of pregnancy to day 0 postpartum or day 5 postpartum, via drinking water. On these days, pups were sacrificed, collecting the blood to determine the concentration of lead by graphite furnace atomic absorption spectrophotometry. Brains were used to determine the total content of nucleic acids, DNA/RNA ratio and the total amount of proteins, lipids and monoamines.

Hepatic resuscitation after warm anoxia: one approach for increasing the donor pool for liver transplantation.

The deleterious effects of warm anoxia on the liver are seen to be irreversible if cooling and transplantation (LT) follow immediately after. The aim of our study is to demonstrate that livers subjected to anoxia may be suitable for LT if a period of resuscitation is interposed before the cooling process. Forty female Large White pigs were used.