THE EFFECT OF HIGH INTENSITY WHITE NOISE ON THE ULTRASTRUCTURE OF AXO-DENDRITIC SYNAPSES IN COLLICULUS INFERIOR OF ADULT MALE CATS. QUANTITATIVE ELECTRON MICROSCOPIC STUDY.

Environmental noise is a serious problem for the society and medicine. Chronic loud noise is known to produce numerous adverse effects on different levels of the organism. In addition to behavioral changes, the involvement of different regions of the brain was documented. The analysis of structural modifications provoked by noise in brain give the possibility to suggest that one of the effects of noise may be the alterations in neurotransmission. Therefore, of special interest should be the elucidation of the effects of chronic noise on the fine structure of synapses of brain areas participating in the processing of auditory information. In the present study, using transmission electron microscope. We elucidate the effects of high intensity chronic white noise on the morphology of axo-dendritic synapses, and size and diameter of synaptic vesicles in auditory region, inferior colliculus of adult male cats. Experimental animals were exposed to 100 dB (5-20 kHz) white noise for one hour per day, for 10 consecutive days. On 11th day, after special procedures, the area of interest was examined under electron microscope. In ~ 15% large synaptic terminals the clustering of synaptic vesicles, as well as swelling, partial vacuolization or degeneration of presynaptic mitochondria were detected. Morphometric analysis of docked (with presynaptic membrane) and undocked synaptic vesicle size revealed that docked vesicles are smaller than undocked vesicles. It was observed in both control and experimental animals, however, in experimental animals, such difference was more significant. Such results suggest that due to continuous transmission, the majority of vesicles are unable to replenish their cargo via transporters. Evaluation of synaptic vesicles size undertaken in the current electron microscopic study has advanced the understanding of the pathophysiology of white noise exposure on auditory brain processing regions, in addition to our understanding of fractional neurotransmitter release at the nerve terminal and on overall brain function.

EFFECT OF ARSENIC EXPOSURE ON BEHAVIOR OF RATS OF VARIOUS AGE GROUPS.

Arsenic is ranked first among toxicants posing a significant potential threat to human health based on known or suspected toxicity. Recent animal studies suggest that the brain is the major target of arsenic exposure. The present study demonstrates the effect of Arsenic compounds on behavior changes in different age (young and adult) groups of rats. In order to study anxiety behavior, learning and memory processes we used open field, elevated plus maze, spontaneous alteration behavior and multi-branched maze tests. Our experiments revealed that 68 mg/L (35 ppm) Sodium (meta) arsenite (when animals got arsenic from drinking water for three months) induces more significant effect on body weight gain in adult rats rather than in young ones. Arsenic exposure may result in rat's emotional instability despite the animals' age. According to the spontaneous alteration test, obtained data revealed that behavior is changed only in adult rats compared to control ones. Also it was found that Arsenic consumption at the same concentration induces considerable difficulties in learning process (multi-branched maze test results) in the adult arsenic exposed group. We have found differences in maze test performance, during fulfilling memory tasks by arsenic exposed animals in comparison to control ones. This distinction was mostly notable in young groups. These data show that Arsenic exposure affects short-term memory more dramatically in adult animals rather than of young ones, whereas difficulties in long-term memory were detected among young animals.

Effect of chronic inhalation of toluene on behavior of rats of various age groups in multi-branched maze.

The effect of a 40-day toluene inhalation on learning of young and adult rats was examined in a multi-branched maze. Experimental rats of both age groups needed more time to pass the maze and made more errors than controls. This impairment was observed in young rats immediately after termination of toluene inhalation and in adult rats immediately and 90 days after toluene.

[Effect of short-term manganese chloride intoxicatuion on anxiety and fear of young rats].

Manganese is an essential trace element for all living organisms. Though some neurological dysfunction take place during intoxication caused by excessive exposure of this metal. The goal of this research was to elucidate the emotional state, in particular anxiety and fear in three groups of young male rats. Two groups of 30 day old rat pups were given drinking water with MnCl(2)·4H(2)O dissolved in, the doses were 1mg/ml (I group) and 10 mg/ml (II group), and the third group was control animals. Before starting and a day after of termination manganese consumption the animals were tested in the "open field" and "elevated-plus maze". In two month old rat pups compared to one month ones the elevation of anxiety was observed that led to increase of fear. 30 day intoxication of one month old rat pups with both doses of manganese (1 and 10 mg/ml) induces: strengthening of motor and orienting-explorative activity, decrease in the level of anxiety and fear. During the intoxication of animals with above mentioned doses of manganese chloride the dose-dependant effect is not observed.

Ultrastructure of hippocampal field CA1 in rats after status epilepticus induced by systemic administration of kainic acid.

The ultrastructure of hippocampal field CA1 in rats was studied 14 days after status epilepticus induced by administration of kainic acid. Structural changes were seen in 40% of cells, predominantly interneurons, which showed both reversible changes (mitochondria with an electron-dense matrix or small numbers of short cristae, moderate dilation of rough endoplasmic reticulum (RER) cisterns, and small numbers of ribosomes) and more significant abnormalities: swollen mitochondria with very small numbers of cristae, which were partially degraded, some with damaged mitochondrial membranes, along with pathologically damaged RER components and focal or peripheral chromatolysis. Chromatolyzed areas sometimes contained membrane-like includes and vacuoles. In addition, the neuropil contained occasional large osmiophilic formations surrounded by astrocyte processes with accumulations of glycogen or gliofibrils. Synaptoarchitectonics were also altered. Asymmetrical synapses were often seen on small dendrites and spines, with highly osmiophilic postsynaptic zones, their synaptic terminals containing numerous synaptic vesicles and large vesicles with electron-dense cores. Some presynaptic endings showed clear signs of classical dark-type degeneration. As the nucleus remained intact in all types of altered neurons, it appears that most cells underwent pathological changes of the necrotic type.

Effect of nadolol injected prior to CRH on stress-induced plasma corticosterone level in rat.

The proposed research is the part of our investigation of the role of catecholamines in the alterations provoked by stress. Especially, we elucidate if Nadolol injected prior to CRH ICV has some effect on plasma corticosterone level. 15 mg/kg of Nadolol (the dose sufficient to prevent CRH-induced increases in heart-rate for 2 hr), dissolved in saline was administered intraperitoneally, 30 minutes prior to CRH (The dose of interest for CRH - 1 mkg/kg - was determined earlier, as provoking the maximal increase of plasma corticosterone level after 20 minutes of its ICV injection). Whole blood was collected at 11.00 am, via indwelling jugular catheter at 0 (control) and 15 minutes after Nadolol injection, also 30 and 60 min after CRH injection. After centrifugation the plasma level of corticosterone was essayed using ELISA method. 15 minutes after Nadolol injection the level of plasma corticosterone in comparing with control wasn't changed, at subsequent time-points plasma corticosterone level was increased but significant difference was observed only after 30 minutes. Thus, according our results, 30 min after injection, the dose of Nadolol, sufficient to prevent CRH-induced increase in heart rate, doesn't preclude the CRH-induced increase of plasma corticosterone - one of key signs of the stress-axis activation. The results were discussed.

[Quantitative analysis of gliocytes and macrogliocyte-neuronal ratio in the rat hippocampus after kindling].

Gliosis is one of the main morphological correlates of epilepsy. It is presented predominantly by proliferation and hypertrophy of astrocytes and activated microglia (macrophages) and is most characteristic to those areas of the epileptogenic zones, where the loss of neurons is significant. One of such structures is the hippocampus, the sclerosis of which develops already at the early stages of epileptogenesis. Using the slides stained with cresylviolet, the quantitative analysis of gliocytes and of macrogliocyte-neuronal ratio was performed in all the areas of the hippocampus 14 and 30 days after electrical kindling. After both time intervals, the decrease of the number of neurons and the increase of the number of gliocytes were found in all the regions of the hippocampus. After 14 days the changes of gliocytes were particularly significant in the radial and oriental layers of the Ammon's horn, after 30 days they were also pronounced in CA3 pyramidal cell layer of and in hilus. Thus, hippocampal gliocytes are actively involved in the epileptogenesis.

Morphological changes and manganese content in the brains of rat pups subjected to subchronic poisoning with manganese chloride.

Morphological changes in neurons and the distributions of nerve and glial cells were studied, the glial index was calculated, and manganese (Mn) contents were determined in the caudate nucleus, the nucleus accumbens, the dorsal and ventral septal nuclei, and the frontoparietal areas of the cerebral cortex in the 40-day-old offspring of rats given different doses (10 and 20 mg/kg) of manganese chloride (MnCl2.4H2O) 15-20 days before pregnancy, during pregnancy, and for one month after parturition with the first portion of food. Mn poisoning increased Mn contents in the brains of rat pups, damaged a small proportion of neurons, and produced marked gliosis. These changes are believed to underlie previously described impairments to learning processes and emotional state in rat pups.

[Morphological changes and manganese level in the brain of rat pups subjected to subchronic manganese chloride intoxication].

The morphological alterations in the neurons together with the distribution of the neural and glial cells were studied, the glial index was calculated, and manganese level was determined in n. caudatus, n. accumbens septalis, n. dorsalis and ventralis septalis, and in the fronto-parietal region of the brain cortex in the 40-day old offspring of the rats, which were given a various daily dose (0, 10, and 20 mg/kg) of manganese chloride (MnCl2 x 4H2O) with the first portion of their food 15-20 days prior to pregnancy, during the pregnancy and for one month after the parturition. Manganese intoxication induced elevation of the manganese level in the brain of the pups with the injury of a small portions of the neurons and a pronounced gliosis. We believe that these changes underlie the previously reported disorders in learning processes and emotional state of the pups.

Kindling-induced hippocampal cell death in rats.

Quantitative analysis of the main cells and interneurons in different layers and fields of Ammon's horn, the hilus, and dentate gyrus was performed two weeks and one month after kindling, i.e., specific electrical stimulation of the ventral hippocampus. At both experimental time points, cells numbers were significantly decreased at all levels of the areas studied except the marginal layer of field CA4. Thus, in this model of experimental epilepsy, the process of epileptogenesis involved both interneurons and main cells in the hippocampus. The possible reorganization of intrahippocampal circuits and their involvement in the increased excitability characteristic of epilepsy are discussed.

[Hippocampal cell loss in rats as a result of kindling].

Quantitative analysis was performed to evaluate the numbers of principal cells cells and interneurons in differenet layers and areas of the horn of Ammonis, hilus and dentate gyrus 2 weeks and 1 month after kindling--specific electrical stimulation of ventral hippocampus. After both experimental time intervals, a significant cell loss was found in all the layers and areas studied, with the exception of stratum oriens of CA4. Thus, in this model of experimental epilepsy, both interneurons and principal cells were found to be involved in the process of epileptogenesis. Different possibilities of reorganization of intrahippocampal circuits and their participation in increased excitability, typical to epilepsy, are discussed.

[The influence of myo-inositol on the ultrastructure of hippocampal CA1 area in kainate treated rats].

The ultrastructure of neurons, synapses and astrocytes of hippocampal CA1 area in rats was investigated 14 days after: systemic injection of kainic acid and kainic acid and myo-Inositol. After injection of kainic acid numerous neurons with superficial and deep ultrastructural changes of cytoplasmic organelles were described. Among synapses numerous forms with osmiophilic active zone and single synaptic vesicles, also presynaptic terminals with core vesicles were often seen. After kainic acid + myo-Inositol injection the cells with superficial changes of organelles dominated and the synapsoarchitectonics of the area was close to normal. Thus, electrono-microscopic data indicate possible neuroprotective (antiepileptic?) features of myo-Inositol.

[Changes in the ultrastructure of neuroglia in some regions of the rat brain in manganese chloride poisoning]. / Izmeneniia ul'trastruktury neroglii nekotorykh oblastei golovnogo mozga krysy pri intoksikatsii khloristym margantsem.

Ultrastructure of astrocytes, olygodendrocytes and microgliocytes of caudate nucleus, substantia nigra and frontoparietal area of the cortex were studied under the influence of the everyday peroral treatment with MnCl2.4H2O during 30 days. Experimental animals were divided into two groups. Animals from the first group received 20 mg/kg of MnCl2.4H2O while for animals from the second one the dose made 50 mg/kg. Animals were killed on days 30 and 120 of the experiment. It was demonstrated that chloride manganese intoxication influences the ultrastructure of all types neuroglial cells, the majority of both macro- and microgliocytes remaining in normal state. Cytotoxic effect of manganese ions on astrocytes manifests in mitochondria destruction, widening of canaliculi and endoplasmic net cisterns, glycogenic granules accumulation, which leads to reduction of oxidative processes level in the nervous tissue. Increased phagocytic activity of the astrocytes was displayed in conditions of relatively high doses of MnCl2.4H2O. Microgliocyte reaction was distinctly dose-dependent and was manifested through their phagocytary activity increase. Oligodendrocytes were most stable to chloride manganese influence.

[Changes in the rat cerebral cortex ultrastructure following peroral administration of manganese chloride]. / Izmeneniia ul'trastruktury kory bol'shogo mozga krysy pri peroral'nom vvedenii khloristogo margantsa.

The effect of 30 days treatment with MnCl(2).4H2O (50 mg/kg in doze) on neuron ultrastructure and interneuronal contacts of cerebral cortex frontoparietal area was studied in rat. The material for the research was taken on 1st (group 1) and 4th (group 2) month of the experiment. Changes in neurons and cortex synapses were less significant than those in subcortical structures. In 1st group of experimental animals neurons displayed vacuolar system hyperplasia and swelling of a part of mitochondria. Changes in synapses were heterogenous from reduction of synaptic vesicles number and mitochondria swelling to degeneration after "dark" type. Despite the fact that intoxication with MnCl(2).4H2O was over, changes in cortical neurons in group 2 were significant although no cells with signs of reorganization were observed. In neuropil of rats from group 2 reduced number of synaptic vesicles as well as reorganized endings filled with amorphous osmiophilic content were encountered more often as compared to animals from group 2.