The oxidative action of quinolinic acid (QUIN), and the protective effects of glutathione (GSH), and 2-amino-5-phosphonovaleric acid (APV), were tested in rat brain synaptosomes, Reactive oxygen species (ROS) formation was quantified after the exposure of synaptosomes to increasing concentrations of QUIN (25-500 microM). The potency of QUIN to induce lipid peroxidation (LP) was tested as a regional index of thiobarbituric acid-reactive substances (TBARS) production, and the antioxidant actions of both GSH (50 microM) and APV (250 microM) on QUIN-induced LP were evaluated in synaptosomes prepared from different brain regions. QUIN induced concentration-dependent increases in ROS formation and TBARS in all regions analyzed, but increased production of fluorescent peroxidized lipids only in the striatum and the hippocampus, whereas both GSH and APV decreased this index. These results suggest that the excitotoxic action of QUIN involves regional selectivity in the oxidative status of brain synaptosomes, and may be prevented by substances exhibiting antagonism at the NMDA receptor.
The atmospheric pressure glow discharge (APGD) is a new type of the discharge discovered by OKAZAKI et al.[l] recently. The APGD can be used in practical application (e.g. ozone generation), but the phenomena occurring in the discharge are not fully understood. We studied the APGD driven at 50 Hz, applied voltage up to 5 kV and burning in helium, argon and nitrogen. We used a planar configuration of discharge cell:electrode. Between the metal electrode and the dielectric plate a fine metal mesh was placed. For each gas we recorded the time dependence of power supply voltage and the time dependence of charge transferred through the discharge. We recorded also the discharges by the CCD camera with a video recorder. The same measurements were done in case of the discharge cells without the metal mesh. The metal mesh changes the discharge significantly. In the case of discharge cell with the mesh we can observe a homogeneous discharge and only one peak in the discharge current per half cicle of applied voltage while in the case of the discharge without mesh we observed individual micro-discharges and many pulses in the current per half cycle. This effect is most obvious in helium.In order to explain the observed phenomena we calculated the electric field in the discharge cell for APGD and propose a possible explanation of APGD. It has been found that the mesh does not influence the electric field in the discharge gap. Thus we propose that the mesh could influence the discharge by its electrical resistance, which is higher than the resistance of the metallic electrode.
Studies suggest age- and sex-dependent structural and functional patterns of human cerebral lateralization underlie hemisphere specialization and its alterations in schizophrenia. Recent works report sexual dimorphism of neurons in the hippocampal formation and specialization of hemispheres in rats. Our experiments indicate for the first time functional lateralization of the high-affinity choline uptake (HACU) system directly associated with a synthesis of acetylcholine in the hippocampus of Wistar rats. The markedly increased HACU activity was found in the left compared to the right hippocampus of adult male but not female animals. Lineweaver-Burk plot analysis revealed a statistically significant increase of Vmax in the left hippocampus of 14-day-old when compared to 7-day-old males. It appears that laterality of HACU occurs during late postnatal maturation, and its degree is markedly enhanced after puberty and attenuated during aging. Quinolinic acid (QUIN), an endogenous agonist of N-methyl-D-aspartate type glutamate receptors, was used in this study to evaluate the neurodevelopmental hypothesis of schizophrenia. It is known that elevated levels of QUIN accompany viral infections, increasing the risk of developing schizophrenia. Bilateral intracerebroventricular application of QUIN (250 nmoles/ventricle) to pups aged 12 days significantly impaired the cholinergic hippocampal system of adolescent male and female rats and reversed lateralization of male HACU. Morphological analysis indicated marked changes in brain lesion sizes (extensive 24 h and moderate 38 days after the operation). Asymmetry of lesions was observed in the majority of cases, but the left hemisphere was not generally more vulnerable to QUIN effects than the right side. Moreover, no lateral differences were found between lesioned hippocampi in the specific binding of [3H]hemicholinium-3 (10%-15% loss of binding sites when compared to sham-operated animals). In summary, our results indicate a symmetrical drop in the number of choline carriers of lesioned male rats but a asymmetrical decrease in the activity of remaing carriers, suggesting defects in processes of sexual brain differentiation, leading under normal conditions to the higher activity of carriers in the left hippocampus. The data demonstrate viral infection-mediated alterations in normal patterns of brain asymmetry and are discussed in relation to animal models of neurodevelopmental and neurodegenerative diseases.
There is accumulating evidence that disturbances in N-methyl-D: -aspartate receptor (NMDA-R) functioning are associated with the pathogenesis of schizophrenia. To assess actual changes in the expression of the GluN1 subunit and its isoforms, we measured absolute differences in the levels of mRNA/protein for panGluN1 (eight isoforms altogether) as well as the mRNA individual isoforms in the postmortem left/right hippocampus of patients with schizophrenia in comparison with non-psychiatric subjects. There were no significant differences in the panGluN1 subunit mRNA expression, but the absolute left/right differences were much more pronounced in the patients with schizophrenia. Protein levels of the GluN1 subunit in the left hippocampus in male schizophrenic patients were lower than controls. The expression of the NR1-4b isoform was attenuated in the left, whereas the NR1-2b was reduced in the right hippocampus of schizophrenic patients. Isoforms associated with the efficiency of NMDA-induced gene expression and with phosphorylation occurred more commonly in schizophrenic hippocampi. In summary, our study suggests that NMDA-R hypofunction in schizophrenia might be selectively dependent on the dysregulation of GluN1 subunit expression, which exhibits a somewhat different expression in the left/right hippocampus of psychotic patients.
Schizophrenia is ranked among multifactor diseases in whose pathogenesis, besides environmental factors, an interplay of functional polymorphisms of a larger number of candidate genes is involved. Neurodevelopmental abnormities are among the most accepted hypotheses in the etiology of schizophrenia. Recently, the role of oligodendrocytes in the development of the cortex has been cited repeatedly. During their various phases of differentiation oligodendrocytes present on their surfaces diverse receptors, among others the mu-opioid receptor (OPRM1). The study was focused on the relationship between the functional A118G polymorphism of the OPRM1 gene (rs1799971) and schizophrenia in groups of 130 male patients and 452 male controls. An association study revealed yet unpublished statistically significant difference of allelic and genotypic frequencies between the control and patient groups. According to our present knowledge, we assume that the OPRM1 gene polymorphism can influence the myelination of CNS neurons through regulations of expression of OPRM1 receptors on surfaces of oligodendrocytes. The neuronal myelination seems to be one of the important factors in the pathogenesis of schizophrenia.
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