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INTRODUCTION: An imbalance in excitatory/inhibitory neurotransmission has been implicated in the pathogenesis of autism. AIM(S): We tested this hypothesis by measuring with Magnetic Resonance Spectroscopy (MRS) and Nuclear Magnetic Resonance (NMR) the content of glutamate (Glu), glutamine (Gln) and GABA in the rat hippocampus in two pharmacological models of autism. METHOD(S): The rat females at the...
INTRODUCTION: The disorders of the glutamatergic neurotransmission have been implicated in the pathogenesis of autism, but data on brain content of glutamate (Glu) in patients and animal models are inconsistent. AIM(S): Aim of this study is to evaluate changes in the brain content of Glu, glutamine (Gln) and GABA in the rat models of pharmacologically-induced autism. METHOD(S): The rat females at...
There are alarming reports on cytotoxicity of the brominated flame retardant tetrabromobisphenol A (TBBPA) in the in vitro cellular models, that seem to be mediated by increases in the intracellular calcium concentration ([Ca2+] i) and oxidative stress. Still, the mechanisms of both these phenomena, their mutual cause‑and‑effect relationships and implication in the TBBPA-induced neuronal death are...
Previous studies have demonstrated that repeated submission of rats to mild hypobaric hypoxia reduces the persistent behavioral and hormonal depressive symptoms induced by exposure to footshock in the learned helplessness paradigm. The aim of this study was to determine whether hypoxic preconditioning of mice can also induce antidepressant- and anxiolyticlike effects that are detectable with the other...
BACKGROUND AND AIMS: Brominated flame retardant tetrabromobisphenol A (TBBPA) contaminates the environment and displays cytotoxic potential. The mechanism of its cytotoxicity in neurons encompasses interference with NMDA and ryanodine receptors (NMDARs and RyRs) resulting in increase in intracellular Ca2+ concentration (Ca2+i), and induction of oxidative stress, which may be primary, or secondary...
BACKGROUND AND AIMS: The results of early studies suggested a role of glutamate receptors in the mechanism of increases in intracellular Ca2+ concentration ([Ca2+]i ) and cytotoxicity induced by the brominated flame retardant, tetrabromobisphenol-A (TBBPA). Although now interest has focused mainly on TBBPA-induced Ca2+ release from intracellular stores, here we revisited the former issue and tested...
Preconditioning is an experimental strategy for reducing ischemic brain damage. There are reports that brief exposure of neurons to NMDA-receptor antagonists may be an adequate preconditioning stressor. We studied effects of preconditioning of the cerebellar granule cells (CGC) in primary culture by 30-minute exposure to NMDA receptor antagonists 0.5 ^M MK-801 or 5 ^M memantine. CGC were challenged...
The aim of this study was to identify, among selected environmental toxins, the substance with the highest in vitro toxicity to neurons combined with the most marked induction of calcium imbalance, oxidative stress and mitochondrial dysfunction. Exposure of primary cultures of rat cerebellar granule cells for 30 min to polychlorinated biphenyls (PCBs) or brominated flame retardants (BFRs) at concentrations...
1,2,3,4,-Tetrahydroisochinolines (TIQ) are endogenous substances present in brain in low concentrations. Several TIQ derivatives are neurotoxic producing a Parkinson’s syndrome. In turn 1-methyl-1- ,2,3,4,-tetrahydroisochinoline (1MeTIQ) was found to reduce neuronal death in various models of neurotoxicity. Our previous results revealed that 1MeTIQ reduces excitotoxicity in the primary culture of...
Tetrabromobisphenol A (TBBPA) is a brominated flame retardant considered as the environmental toxin affecting the brain. The exact molecular mechanisms of the TBBPA-induced neurotoxicity are unclear, however recent studies suggest a role of the NMDA receptor-mediated excitotoxicity and/or of calcium imbalance. To verify this hypothesis in the present study we examined relation between toxicity of...
Various endogenous teterahydroisochinoline derivatives present in the mammalian brain have been considered as neurotoxic substances. However 1-methyl-1,2,3,4-tetrahydroisochinoline (1MeTIQ) is known for its mild neuroprotective potential of the unclear mechanism. On the one hand 1MeTIQ exhibits anti-dopaminergic activity and reduces the neurotoxic effects of MPTP and rotenone, decreasing also the...
1-Methylnicotinamide (MNA) is a key metabolite of nicotinamide, which is an important cofactor in many metabolic pathways with intrinsic cytoprotective properties. Recent studies demonstrated that MNA induces in the periphery the anti-inflammatory and vasoprotective effects mediated by the COX-2/ PGI2 signaling pathway. The role of this pathway in the protection against ischemic injury has been emphasized...
Thimerosal (TH), an ethylmercury complex of thiosalicylic acid has been used as preservative in vaccines. In vitro neurotoxicity of TH at high nM concentrations has been reported. Although a number of toxicological experiments demonstrated high affinity of mercury to thiol groups of the extracellular amino acids and proteins that may decrease concentration of free TH in the organism, less is known...
Previous in vivo and in vitro studies demonstrated neuroprotective potential of pretreatment with 1α, 25-dihydroxyvitamin D3 (calcitriol). The aim of present study was to determine effectiveness of calcitriol administered in vivo after brain ischemic episode in the rat model of perinatal asphyxia, or co-applied with some delay during 24 h exposure to glutamate of the mice hippocampal, cortical and...
Controlled fl uctuations in intracellular calcium concentrations play an important role in many cellular processes such as muscle contraction, secretion, metabolism, and neuronal function. Ryanodine receptors (RyR) are intracellular ion channels that mediate the release of calcium ions from internal stores and have been suggested as pharmacological targets for heart disease and neurodegenerative diseases...
The aims of this study were (1) to characterize calcium signaling in rat cortex induced by repeated in vitro application of the glutamatergic agonists L-glutamate, NMDA, AMPA and DHPG, (2) to analyze the influence of transient severe hypobaric hypoxia (180 Torr) administered in vivo on calcium responses to stimulation of glutamate receptors by their agonists, and (3) to evaluate the effects of preconditioning...
Nicotinamide is an important cofactor in many metabolic pathways and a known neuroprotective substance, while its methylated product, 1-methylnicotinamide, is a suspected neurotoxin. Homocysteine is a risk factor in Alzheimer’s disease and neurodegeneration, causing inhibition of methylation processes and inducing excitotoxicity. In this study, using primary cultures of rat cerebellar granule cells...
Nicotinamide is an important cofactor in many metabolic pathways and a known neuroprotective substance, while its methylated product, 1-methylnicotinamide, is a suspected neurotoxin. Homocysteine is a risk factor in Alzheimer's disease and neurodegeneration, causing inhibition of methylation processes and inducing excitotoxicity. In this study, using primary cultures of rat cerebellar granule cells...
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