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ABSTRACT: The cardiovascular protecting effects of resveratrol, an antioxidant polyphenol present in grapes and wine, have been attributed to its vasorelaxing effects and to its anti-inflammatory, antioxidant, and antiplatelet actions. Inhibition of adrenal catecholamine release has also been recently implicated in its cardioprotecting effects. Here, we have studied the effects of nanomolar concentrations of resveratrol on quantal single-vesicle catecholamine release in isolated bovine adrenal chromaffin cells. We have found that 30 to 300 nM concentrations of resveratrol blocked the acetylcholine (ACh) and high K(+)-evoked quantal catecholamine release, amperometrically measured with a carbon fiber microelectrode. At these concentrations, resveratrol did not affect the whole-cell inward currents through nicotinic receptors or voltage-dependent sodium and calcium channels, neither the ACh- or K(+)-elicited transients of cytosolic Ca(2+). Blockade by nanomolar resveratrol of secretion in ionomycin- or digitonin-treated cells suggests an intracellular site of action beyond Ca(2+)-dependent exocytotic steps. The fact that nanomolar resveratrol augmented cGMP is consistent with the view that resveratrol could be blocking the quantal secretion of catecholamine through a nitric oxide-linked mechanism. Because this effect occurs at nanomolar concentrations, our data are relevant in the context of the low circulating levels of resveratrol found in moderate consumers of red wines, which could afford cardioprotection by mitigating the catecholamine surge occurring during stress.
Molecular pharmacology 10/2010; 78(4):734-44. · 4.53 Impact Factor
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ABSTRACT: 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. The present results demonstrate that maternal exposure to 10mg/l of Cd leads to neurochemical disturbances on serotoninergic and aminoacidergic systems during development.
Environmental toxicology and pharmacology. 01/2010; 29(1):87-90.
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ABSTRACT: 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.
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.
Reducing maternal corticosterone (mCORT) during gestation led to alterations in dopamine and serotonin levels in all three brain areas studied at PN 23. Alterations persisted until at least PN 90 in the serotonergic systems; the dopamine content of the hippocampus also remained modified. Reduced mCORT during gestation also led to alterations in the development and maturation of the hypothalamic noradrenergic systems. Sexually dimorphic responses were observed in all these monoaminergic systems at different times.
These results suggest that while they are still developing, brain monoaminergic systems are particularly sensitive to epigenetic influences. An adequate foetal level of CORT is required for the normal ontogeny of brain monoaminergic systems. The present data also provide that during the critical period of brain development, maternal CORT plays an important role in the sexual differentiation of monoaminergic systems, with particular influence on brain serotonergic neurones.
Acta Physiologica 08/2009; 197(4):333-40. · 3.09 Impact Factor
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ABSTRACT: The mechanism of the neuroprotective action of the tetracycline antibiotic minocycline against various neuron insults is controversial. In an attempt to clarify this mechanism, we have studied here its effects on various electrophysiological parameters, Ca(2+) signalling, and glutamate release, in primary cultures of rat hippocampal neurons, and in synaptosomes. Spontaneous excitatory postsynaptic currents and action potential firing were drastically decreased by minocycline at concentrations known to afford neuroprotection. The drug also blocked whole-cell inward Na(+) currents (I(Na)) by 20%, and the whole-cell Ca(2+) current (I(Ca)) by about 30%. Minocycline inhibited glutamate-evoked elevation of the cytosolic Ca(2+) concentration ([Ca(2+)](c)) by nearly 40%, and K(+)-evoked glutamate release from synaptosomes by 63%. Minocycline also depressed the frequency and amplitude of spontaneous excitatory postsynaptic currents, but did not affect the whole-cell inward current elicited by gamma-aminobutyric acid or glutamate. This pharmacological profile suggests that the neuroprotective effects of minocycline might be associated with the mitigation of neuronal excitability, glutamate release, and Ca(2+) overloading.
European Journal of Neuroscience 12/2007; 26(9):2481-95. · 3.63 Impact Factor
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ABSTRACT: 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.-administered to gestating mothers, on the maturation of the aminoacidergic systems of their offsprings' brains. gamma-Aminobutyric acid (GABA) and glutamate concentrations were determined in male and female offspring at postnatal days (PN) 23 and 90 in four brain areas: the hippocampus, hypothalamus, striatum and cortex. The activity of glutamic acid decarboxylase (GAD), the most important enzyme in the synthesis of GABA, was also analysed. The results show that a reduction in maternal corticosterone during gestation leads to a reduced GABAergic content in all brain areas studied at PN23; permanent organizational changes occurred in the cortex, striatum and hypothalamus. Maternal metyrapone treatment also affected the development of the glutamatergic systems, females being more affected than males at both PN23 and PN90 particularly in the hypothalamus and cortex. The metyrapone treatment produced no changes in GAD activity at PN23, but induced an important increase in this activity at PN90.
International Journal of Developmental Neuroscience 12/2007; 25(7):465-71. · 2.42 Impact Factor
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ABSTRACT: The mechanism of the neuroprotective action of the tetracycline antibiotic minocycline against various neuron insults is controversial. In an attempt to clarify this mechanism, we have studied here its effects on various electrophysiological parameters, Ca2+ signalling, and glutamate release, in primary cultures of rat hippocampal neurons, and in synaptosomes. Spontaneous excitatory postsynaptic currents and action potential firing were drastically decreased by minocycline at concentrations known to afford neuroprotection. The drug also blocked whole-cell inward Na+ currents (INa) by 20%, and the whole-cell Ca2+ current (ICa) by about 30%. Minocycline inhibited glutamate-evoked elevation of the cytosolic Ca2+ concentration ([Ca2+]c) by nearly 40%, and K+-evoked glutamate release from synaptosomes by 63%. Minocycline also depressed the frequency and amplitude of spontaneous excitatory postsynaptic currents, but did not affect the whole-cell inward current elicited by -aminobutyric acid or glutamate. This pharmacological profile suggests that the neuroprotective effects of minocycline might be associated with the mitigation of neuronal excitability, glutamate release, and Ca2+ overloading.
European Journal of Neuroscience 10/2007; 26(9):2481 - 2495. · 3.63 Impact Factor
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ABSTRACT: 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. These findings suggest that estradiol acts as a neuroprotectant--but not as a neuroreparatory agent--and that it might be able to attenuate striatal dopaminergic neuron degeneration caused by neurotoxic agents.
Toxicology 12/2004; 204(2-3):155-60. · 3.68 Impact Factor
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ABSTRACT: 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.
Developmental Brain Research 05/2004; 149(2):153-6. · 1.78 Impact Factor
