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EN
Antisense oligonucleotides (asODN) have recently been used to block specific gene expression in the rodent brain.Their target include subunits of receptors for neurotransmitters, neuropeptides and transcription factors, i.e., those proteins,whose other blocker are not known.Succesful applications of the as ODN require good understanding of their pharmacokinetics, mechanisms of action and side effects in the brain.Unfortunately, very little is known in this regard.Both intraventricular and intrastructure route of administration of phosphorodiester (0-ODN) and phosphorothioate (S-ODN) ODN to the brain were effectvely employed.However doses used,even in the case of the same analog, differ up to two orders of magnitude.Since translation arrest is belived to be an effective mechanism of ODN activity in the brain, most of the authors target the ODN to the mRNA region including the translation codon, but there are most no studies of the target mRNA levels.The paper reviews the recent development in this field, offering critical evaluation of the data.
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issue 3
382-388
EN
Recently, it was found that hydrogen sulfide (H2S) may serve as an important transmitter in peripheral organs as well as in the brain. The aim of the present study was to evaluate the possible function of H2S in the brain regulation of the circulatory system. Experiments were performed on conscious, male, Wistar-Kyoto rats. Mean arterial blood pressure (MABP) and heart rate (HR) were recorded continuously under baseline conditions and during infusions into the lateral cerebral ventricle (LCV) of the experimental animals. In control series LCV infusion of vehicle (Krebs-Henseleit bicarbonate-buffer) did not cause significant changes in MABP or HR. LCV infusion of H2S donor (NaHS) at the rate of 400 nM/h resulted in an increase in MABP, whereas infusions at the rate of 100 nM/h and 200 nM/h failed to change MABP. On the other hand LCV infusion of H2S donor at the rate of 200 nM/h caused a significant increase in HR while infusion at the rate of 400 nM/h produced an increase in HR, which was smaller than this observed during infusion at the rate of 200 nM/h. H2S donor administered at the rate of 100 nM/h failed to affect HR. In conclusion, the present study demonstrates that exogenous hydrogen sulfide changes hemodynamic parameters by centrally mediated mechanisms. The hemodynamic effect seems to be dependent on H2S concentration in cerebrospinal fluid. It appears that the hypertensive response may occur at a concentration, which does not exceed twice the physiological level.
EN
Despite the numerous reports on the role of tumor necrosis factor-alpha (TNF-alpha) in the brain neuropathology, very little is known about the mechanisms by which TNF-alpha may mediate neuroprotection. Different hypotheses pertain to the molecular and cellular effectors triggered by the activation of TNF receptors (TNFRI and TNFR2). They are focused on diminishing the production of nitric oxide and free radicals, alteration of excitatory amino acids neurotransmission, maintenance of neuronal calcium homeostasis and induction of neurotrophic factors synthesis. In this review all these data are summarized. Moreover, possible explanations for the inconsistent data concerning the TNF-alpha effect on neuron are discussed.
EN
Regardless of reason, endothelial cells hypoxia is a primary source of their dysfunction. The result of hypoxia is a damage of endothelium structure, that leads to neurons damage. Parallel to the hypoxia, the protective mechanisms are activated in order to decrease effect of endothelium and neurons damage.
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Content available remote

Role of serotonin in cerebral oxidative stress in rats

100%
EN
Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter synthesized by the aromatic amino acid decarboxylase using 5-hydroxytryptophan (5-HTP) as a substrate. It was recently shown that serotonin and its precursor have powerful antioxidant properties. The aim of this study was to evaluate the effect of reduction in 5-HT levels by para-chlorophenylalanine (pCPA) and their restoration by 5-HTP administration on lipid peroxidation and antioxidant status in rat brain. Serotonin levels were decreased by p-chlorophenylalanine administration. The effect of p-chlorophenylalanine was counteracted by the intraperitoneal administration of 5-hydroxytryptophan. We evaluated the concentration of serotonin, malonyl dialdehyde and the status of antioxidants (GSH, catalase and superoxide dismutase) in brain. The results showed that p-chlorophenylalanine (300 mg/kg) induced a depletion of serotonin concentration and antioxidant status, as well as enhancing malonyl dialdehyde concentration in brain. The exogenous administration of 5-hydroxytryptophan prevented all effects induced by p-chlorophenylalanine in brain tissue. The recovery of the neurotransmitter concentration in brain was related to the reduction of lipid peroxide generation and improved antioxidant status. In conclusion, our study supports the view that the antioxidant properties of serotonin protect against basal oxidative stress in brain.
EN
Histological and autoradiographic studies revealed miotic activity in the subependymal germinal layer in the brains of adult mice. The number of mitoses observed was higher in animals subjected to administration of hematoporphyrin and selenourea
EN
Glutamate is the predominant excitatory neurotransmitter in the central nervous system (CNS) and glutamatergic transmission is critical for controlling neuronal activity. Glutamate is stored in synaptic vesicles and released upon stimulation. The homeostasis of glutamatergic system is maintained by a set of transporters present in plasma membrane and in the membrane of synaptic vesicles. The family of vesicular glutamate transporters in mammals is comprised of three highly homologous proteins: VGLUT1-3. The expression of particular VGLUTs is largely complementary with limited overlap and so far they are most specific markers for neurons that use glutamate as neurotransmitter. VGLUTs are regulated developmentally and determine functionally distinct populations of glutamatergic neurons. Controlling the activity of these proteins could potentially modulate the efficiency of excitatory neurotransmission. This review summarizes the recent knowledge concerning molecular and functional characteristic of vesicular glutamate transporters, their development, contribution to synaptic plasticity and their involvement in pathology of the nervous system.
EN
The biotransformation of endomorphin-1 (EM-1) by brain synaptic membranes has been studied. Peptide fragments of EM-1 that were formed during incubation with membrane preparations in vitro were isolated by High-performance liquid chromatography (HPLC) and characterized using determination of amino acid composition. At pH 7.4, two degradation products, EM-1(1-3) and EM-1(1-2), were identified. EM-1 was degraded 77.5% at 30 min incubation with synaptic membranes. The time course of the experiments and the effect of carboxypeptidase inhibitor (CPI) demonstrated that the proteolysis reaction involves the participation of carboxypeptidase activity.
EN
In vivo microdialysis allows sampling of brain regions in conscious, freely moving animals. Moreover, the in vivo microdialysis allows to administer drugs directly into specific brain areas. Both are useful in behavioral studies. The subject of this review is the methodology of brain microdialysis, that is construction of the probe, effect of temperature, composition of the perfusion medium, perfusion flow rate, characteristics of the membrane material and the role of the diffusion coefficient. Other techniques of the study of in vivo release, alternative for microdialysis, are described. Advantages and disadvantages of acute and chronic microdialysis are discussed. Chronic microdialysis is especially needed in behavioral studies. Finally, the examples of application of microdialysis in behavioral studies of vasopressin (AVP) and oxytocin (OXT) and our own experience in these studies are described.
EN
The activity of rhodanese, 3-mercaptopyruvate sulfurtransferase and g-cystathionase and the content of glutathione and sulfane sulfur compounds were determined in Rana temporaria brain in April. The high sulfane sulfur level observed in the spring seems to be associated with protection against cellular oxidative stress after the period of hibernation with its minimal oxidative metabolism. Key words: sulfane sulfur, sulfurtransferases, glutathione, frog brain
EN
Pairing tactile stimulation of a row of whiskers with a tail shock results in an expansion of the functional representation of the stimulated whiskers within the primary somatosensory cortex of mice. Using the same paradigm, the present study examined field potentials evoked in ex vivo slices of the barrel cortex. The amplitude of responses, evoked by single and repetitive stimuli in layer IV?layer II/III pathway contained within the barrel column corresponding to the whisker stimulated during training, was unchanged. In contrast, in a transcolumnar pathway from the 'trained' barrel to layer II/III of the neighboring, 'untrained' column, the amplitude of responses was reduced and responses to trains of stimuli applied at 40 Hz, but not at lower frequencies, depressed faster. These data are suggestive of a selective weakening of excitatory transmission and/or enhancement of inhibitory transmission in transcolumnar pathways, which accompany associative learning-induced cortical plasticity.
EN
Complement is important to host defense and the regulation of inflammation. The liver is overwhelmingly the major source of circulating complement. However, many other organs are capable of synthesizing some or all of the complement components in a regulated tissue-specific manner. There is increasing evidence that this locally generated complement is biologically active and exerts powerful effects within the local environment. We review the role of local complement synthesis within different organs and speculate on its implication for immune and metabolic functions.
EN
The 7-days shift of M. funereus larvae, from nature to a constant temperature of 23?C led to changes in midgut and brain protein quality and quantity. The changes in midgut protein profiles are characterized by an intensified protein band Mr of 29 kD, the absence of protein Mr of 22 kD and less intense bands Mr of 8.5-2.5 kD. Electrophoretic patterns of brain proteins showed less intense Mr of 66-2.5 kD protein bands.
EN
Six-day-old male rats received a mechanical lesion in the left cerebral hemisphere. Thereafter, a single dose of either 5, 50 or 500 units (U) of recombinant rat interleukin-1beta (IL-1beta) was injected into the lesion cavity. One or 2 days after the injury, the rats were injected with ^3H-thymidine. Brain sections were subjected to BSI-B4 lectin histochemistry and autoradiography to visualise proliferating and non-proliferating macrophages located within the region of injury. A mitogenic effect of IL-1beta on macrophages was observed on day 2 in brains injected with the lowest 5 U dose of cytokine. Following administration of higher 50 U and 500 U doses, infiltration of the injured tissue by macrophages was significantly intensified on day 1. However, on day 2, dose-dependent reductions of the total number of macrophages as well as their proliferative activity were recorded. The findings suggest that the higher the initial quantity of macrophages, the sooner they disappeared from the injury site. It may therefore be hypothesised that IL-1beta-induced increase in macrophage recruitment at the beginning of the inflammatory response speeded the removal of tissue debris and, therefore, accelerated healing of the injured nervous tissue.
17
Content available remote

Calcium signaling in the brain

88%
EN
Calcium ions regulate many processes in the central nervous system via interaction with intracellular calcium-binding proteins. One class of these proteins shares a common structural motif, the EF-hand. A consensus amino acid sequence for this motif has aided the identification of many new members of this family. Some of these proteins, like parvalbumin, calbindin, and calretinin, proved to be useful neuronal markers for a variety of functional brain systems and their circuitries. Their major role is assumed to be buffering, transport of Ca?+, and regulation of various enzyme systems. Cellular degeneration is often accompanied by Ca?+ overload. It has been assumed that neurons containing certain intracellular Ca?+ - binding proteins may have a greater capacity tu buffer Ca?+ and therefore would be more resistant to degeneration.
18
88%
EN
The perirhinal cortex in the dog?s brain is composed of two traditional Brodmann?s areas: 35 and 36. Area 35 is situated along the entire rostro-caudal extent of the fundus of the posterior rhinal sulcus, whereas area 36 occupies its lateral bank. In this study, four subdivisions were distinguished in area 35 based on cytoarchitectonic differentiation. Area 36 is poorly developed in the dog?s brain and was divided into two subdivisions. The most characteristic features of area 35 are: a wide layer I, scattered cell clusters in layer II, and a prominent layer V containing a distinct population of large multiform neurons. Area 36 can be recognized by the presence of numerous cell clusters in layer II and increasing radial arrangement of neurons in deep layers of the area. Two fields of the postrhinal cortex were identified in the additional postrhinal gyrus, which is found in the fundus of the most caudal extent of the posterior rhinal sulcus.
EN
The effects of R(+)-8-Hydroxy-dipropyl-aminotetralin, (R(+)-8-OHDPAT) and R(+)-5-Fluoro-Hydroxy-dipropyloaminotetralin (R(+)-UH-301) injection into the dorsal raphe nucleus (DRN) on fear behavior in a modified version of the light-dark transitions test and regional brain monoamines (NA, DA, 5-HT) and their metabolites ( MHPG, DOPAC, 5-HIAA) in the hypothalamus (HPT), midbrain central gray matter (MID), amygdala (AMY), hippocampus (HIP) and pons (PO) were examined. An injection of R(+)-8-OHDPAT (300 ng) as well R(+)-UH-301 (300 ng) into the DRN evoked i) an increase in the number of head dipping from dark to the illuminated compartment of chamber; ii) an increase of time spent motionless in the dark compartment; iii) decrease of time of locomotion activity in the illuminated compartment. There was no effect on (1) time out from the illuminated to the dark compartment; (2) time of locomotion activity in the dark compartment; (3) time spent motionless in the illuminated compartment; 4) the number of returns from the dark to the illuminated compartment. HPLC analysis showed reduction of 5-HIAA/5-HT ratio in the HPT, HIP and PO, reduction of 5-HT in the MID, increase of NA content in the HPT and AMY, increase of MHPG/NA ratio in the HIP and PO, and increase of DA content in the HPT, AMY and HIP and increase of DOPAC content in the HIP after R(+)-8-OHDPAT injection into the DRN. But injection of R(+)-UH-301 into the DRN reduced 5-HT in the MID and increased in the AMY, reduced 5-HIAA content in the HIP and increased in the MID, reduced NA content in the HIP and increased in the HPT and decreased MHPG/NA ratio in the PO. These results indicate that both 5-HT1A receptor agonists, R(+)-8-OHDPAT and R(+)-UH-301, acting on the 5HT1A autoreceptors caused the anxiolytic effects, reduced fear behavior on the rat connected with infringement of dynamic balance between the serotonergic and catecholaminergics systems.
EN
Nitric oxide (NO) has been found to play an important role as a signal molecule in many parts of the organism. However, under certain conditions, like hypoxia or ischemia, it acts as a cytotoxic effector molecule. It appears paradoxical that NO on the one hand acts as a physiological intercellular messenger and on the other can have damaging effects to cells. To make things even more complicated cytoprotective properties of NO are also described. Whether NO is useful or harmful depends on the rate and location of its production.
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