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S M Zimatkin

Publications and source records attributed to S M Zimatkin.

At least 19 recordsLinked to original sources
PubMed2006

Spatial organization and morphometric characteristics of histaminergic neurons in the rat brain.

We report here a study addressing the spatial organization, densities, numbers, sizes, and shapes of histaminergic neurons in the rat hypothalamus. Studies were performed on 50 rats using histochemical and morphometric methods, computer image analysis, and three-dimensional reconstruction of the histaminergic nuclei of the hypothalamus. The results demonstrated that the total bilateral volume of the histaminergic nuclei of the rat brain amounts to 0.5 mm(3): the E2 nucleus occupies 40% of the total volume, E4 occupies 35%, E3 occupies 13%, E5 occupies 9%, and E1 occupies 3%. The distribution density of monoamine oxidase B neurons in the histaminergic nuclei of the rat hypothalamus decreased in the order E1 > E3 > E2 (the "compact" nuclei) > E4 (an "intermediate" density nucleus) > E5 (the "diffuse part"). The mean number of histaminergic neurons in the rat hypothalamus was 37200 +/- 2800; the E2 nucleus contained 54% of these cells, E3 contained 23%, E4 contained 6%, E1 contained 7%, and E5 contained 0.32%. The E1-E3 nuclei were dominated by small and intermediate-sized neurons, round in shape, and the E5 nucleus was dominated by intermediate and large neurons, fusiform in shape. A subpopulation of giant histaminergic neurons was detected in the E4-E5 nuclei.

Animals↗
PubMed2005

[Spatial organization and morphometric characteristic of histaminergic neurons of the rat brain].

The aim of the study was the estimation of the spatial organization, the density of distribution, number, sizes and shape of histaminergic neurons of the rat hypothalamus. The investigation was carried out in 50 adult Wistar rats, using the methods of histochemistry, morphometry, computer image analysis and 3D reconstruction of hypothalamic histaminergic nuclei. It was found that the total bilateral volume of rat brain histaminergic nuclei was equal to 0.5 mm3 : E2 nucleus occupied 40% of their total volume, while E4 occupied 35%, E3 - 13%, E5 - 9% and E1 - 3%. The density of distribution of monoamineoxidase B-positive neurons was decreased in a series E1 > E3 > E2 (compact nuclei) > E4 (intermediate nucleus) > E5 (diffuse part). The average number of histaminergic neurons in rat hypothalamus was equal to (372 +/- 28) x 10(2): E2 nucleus contained 54% of that amount, E3 - 23%, E4 - 16%, E1 - 7%, E5 - 0.32%. In E1-E3 nuclei, small and medium neurons round in shape were prevalent, while in E5 these were medium and large neurons of fusiform shape. The subpopulation of giant histaminergic neurons was found in E4-E5.

Animals↗
PubMed2003

[The histaminergic brain neuron system].

This review describes the current concepts of distribution, morphological peculiarities and functions of histaminergic structures in human and animal brain. In adult mammals and humans, the perikarya of histaminergic neurons are localized exclusively in the hypothalamus, mainly in its tuberomamillary nuclei, where 5 subgroups are distinguished. It is only there that the syntheses of neuronal histamine takes place and histamine-synthesizing enzyme histidine decarboxylase and corresponding mRNA were found. The processes of histaminergic neurons innervate practically all the brain regions. Histamine action is mediated by three types of receptors: H1, H2 (postsynaptic) and H3 (presynaptic), which are widely distributed in the brain. Histaminergic brain system is involved in the regulation of various functions, systems and reactions of the organism and participates in the pathogeneses of many disturbances and diseases. The review provides the detailed description of the localization of histaminergic neuron perikarya in mammals, the existing classifications of histaminergic neurons of rat brain, the distribution of histaminergic fibers in various brain regions, the organization of human histaminergic brain system, histaminergic neuron ultrastructure, afferent innervation and regulation.

Animals↗
PubMed2002

LPO and ethanol biotransformation systems in the liver as markers of predisposition to ethanol hepatotoxicity.

An original experimental model for detecting organ-specific markers of predisposition to ethanol hepatotoxicity is proposed. A relationship between congenital activity of LPO processes in rat liver (before ethanol intoxication) and the type and severity of ethanol-induced damage to the liver was demonstrated using methods of mathematical modeling. It was proven that intact rats with genetically high MDA levels in the liver and more active systems of MDA generation in ascorbate- and NADPH-dependent reactions are prone to ethanol-induced damage to the liver.

Acetaldehyde↗
PubMed2001

Relationship of brain ethanol metabolism to the hypnotic effect of ethanol. I: Studies in outbred animals.

BACKGROUND: This study was designed to investigate the relationship between the ethanol-oxidizing capacity of the brain, accumulation of acetaldehyde, and ethanol-induced hypnosis in animals in vivo. METHODS: Randomly outbred albino rats were treated with ethanol, and the duration of ethanol-induced loss of the righting response (sleep time) was measured. They were killed 2 weeks later (without further in vivo administration of ethanol), and brain homogenates were prepared to measure the accumulation of acetaldehyde from ethanol added in vitro. In a similar way, we determined the sleep time and, 5 days later, the rates of acetaldehyde accumulation in brains of heterogeneous mice. RESULTS: Significant correlations between the duration of ethanol-induced sleep and acetaldehyde accumulation in vitro were found. The Km value of the process of acetaldehyde accumulation was lower in long-sleeping, as compared with short-sleeping, rats. A similar result was also obtained in genetically heterogeneous mice. Animals with a longer duration of ethanol-induced sleep had a higher level of the accumulation of ethanol-derived acetaldehyde in brain homogenates, as compared with the short-sleeping mice. Rats and mice with the intermediate duration of ethanol-induced sleep had an intermediate value of acetaldehyde accumulation in brain homogenates. There was no correlation between brain catalase activity and ethanol-induced loss of the righting response in either the rats or the mice. CONCLUSIONS: This study is a direct demonstration of the positive correlation between ethanol-derived acetaldehyde accumulation in vitro in the brain and a central (behavioral) effect of alcohol in outbred rats and mice in vivo.

Acetaldehyde↗
PubMed2001

Relationship of brain ethanol metabolism to the hypnotic effect of ethanol. II: Studies in selectively bred rats and mice.

BACKGROUND: To clarify the role of brain acetaldehyde in the hypnotic effect of ethanol, we compared the ethanol-oxidizing capacity (rate of acetaldehyde accumulation) and catalase and aldehyde dehydrogenase activity in the brains of animals genetically selected for different sensitivities to the hypnotic effect of ethanol. METHODS: We used high, low, or control alcohol-sensitive rats (HAS, LAS, and CAS) and short- and long-sleep mice (SS and LS), as well as SS x LS recombinant inbred mice with known strain differences in mean duration of ethanol-induced sleep. We studied the rate of accumulation of acetaldehyde from ethanol in brain homogenates of these animals and correlated those values with their hypnotic sensitivity to ethanol. RESULTS: Acetaldehyde accumulation from ethanol was significantly higher in the brain homogenates from HAS rats and LS mice with high sensitivity to the hypnotic effect of ethanol in vivo, compared with LAS rats and SS mice with low sensitivity to ethanol. A correlation was found between the duration of ethanol-induced sleep and the in vitro rate of accumulation of ethanol-derived acetaldehyde in the brains of recombinant SS x LS mice strains. There was no correlation of sleep time with brain catalase levels. There were no line differences in brain catalase or aldehyde dehydrogenase or in alcohol or aldehyde dehydrogenase activity in livers of LAS, CAS, and HAS rats or in SS and LS mice. CONCLUSIONS: A correlation between the brain acetaldehyde accumulation, but not catalase levels, and the central effect of ethanol was demonstrated in animals genetically differing in initial sensitivity to the hypnotic effect of ethanol.

Acetaldehyde↗
PubMed2000

Thiamine status in liver and brain of rats genetically selected for different sensitivity to hypnotic effect of alcohol.

BACKGROUND: The mechanisms of the different sensitivity or resistance of animals and humans to alcohol are still not completely understood. For further biochemical characterization of animals genetically selected for high-alcohol sensitivity (HAS) and low-alcohol sensitivity (LAS) with the hypnotic effect of alcohol, the thiamine status and thiamine metabolizing enzymes in these animals have been studied. METHODS: We investigated thiamine diphosphate and thiamine triphosphate levels as well as the activity of thiamine-dependent enzyme, transketolase, and thiamine-metabolizing enzymes, thiamine kinase, and thiamine triphosphatase in the liver and brain of HAS, LAS, and CAS (control) rats by standard biochemical techniques. RESULTS: It was found that the activity of transketolase, and the level of the coenzyme form of thiamine, thiamine diphosphate (TDP), were significantly lower in HAS versus LAS rats. The activation of transketolase by the exogenous TDP (TDP-effect) was significantly higher in the liver and brain regions of HAS rats compared with LAS rats. The level of TDP in the liver and cerebellum of HAS rats was significantly lower compared with LAS rats. These results indicate a severe deficiency of TDP in HAS rats. HAS rats have a significantly lower activity of thiamine triphosphatase, the additional source of TDP. Accordingly, HAS rats have much higher thiamine triphosphate levels in the liver and brain, compared with LAS rats. There were no significant differences between groups with respect to the thiamine diphosphatase and thiamine kinase activity. Most of the above parameters had the intermediate values in CAS rats, compared with LAS and HAS rats. These data indicate the possible role of the thiamine phosphate esters and related enzymes in the mechanisms that bring about the differential sensitivity to the hypnotic effect of alcohol. CONCLUSIONS: HAS rats have the genetically mediated thiamine diphosphate deficiency and increased thiamine triphosphate levels, probably due to reduced activity of thiamine triphosphatase in the liver and brain, compared with LAS rats. It can be related with the higher initial sensitivity of HAS rats to hypnotic effect of ethanol.

Alcohol Drinking↗
PubMed1998

Distribution and kinetics of ethanol metabolism in rat brain.

It was found that the accumulation of acetaldehyde produced from 50 mM ethanol in rat brain homogenates takes place in all major brain regions. The velocity varied between 3.5 to 7.1 nmol/mg of protein/hr. The rate increased in the following order: brain hemispheres, striatum, brainstem, hypothalamus, and cerebellum. Significant regional differences in this process were found: in the initial period of incubation (5 min), acetaldehyde accumulation was maximal in the brain hemispheres; but, in the 30- to 60-min period, it became significantly higher in the cerebellum. Inhibition of this process by the catalase inhibitor, 3-amino-1,2,4-triazole (8 mM), was minimal in the brainstem (27%) and maximal (57%) in the cerebellum, despite nearly complete inhibition of catalase. This would indicate that processes other than catalase activity must contribute to acetaldehyde accumulation.

Acetaldehyde↗
PubMed1997

Alcohol consumption alters monoamine oxidase activities in brain structures: relation to ethanol craving.

BACKGROUND: In spite of numerous biochemical studies the role of brain monoamine oxidase (MAO, EC 1.4, 3.4) in the mechanisms of central alcohol action and the pathogenesis of alcoholism remains unclear. The possible reason of that is the highly heterogeneous distribution of the enzyme in a brain and the different direction of alcohol-induced changes of MAO in various morphological structures. Therefore we used the histochemical approach for examination of the effect of chronic alcohol consumption on MAO A and B activities in definite brain structures: various types of aminergic neurons, glial cells and blood capillaries. METHODS AND RESULTS: For 6 months 180 inbred male rats consumed 15% ethanol as the only source of drinking (mean alcohol consumption was 6 g/kg/day). On the 5-6th months of the experiment animals with maximal (ethanol preferring, EP) or minimal (water preferring, WP) alcohol craving were chosen by testing for free choice between 15% (v/v) ethanol solution and water (3 times, during 2 days, at 2-week intervals). The animals chosen were sacrificed and brain samples were studied by our quantitative histochemical method (23). It was found, that chronic ethanol consumption induced dramatic disturbances in MAO activities in the brain structures strongly depending on the alcohol preference of animals. The total MAO activity in WP rats decreased or remained unchanged, but in EP rats it dramatically increased, especially in neurons of n. raphe pontis and n. raphe dorsalis (1.198 +/- 0.028 and 1.268 +/- 0.018 units as compared to control values 0.594 +/- 0.008 and 0.804 +/- 0.011 units; p < 0.001). MAO A activity in all brain structures containing both forms of the enzyme was increased, especially in EP rats: up to 3 times in neurons of the n. raphe pontis from 0.134 +/- 0.003 units in control to 0.541 +/- 0.013 units; p < 0.001). At the same time in the neurons containing only MAO A activity (n. olivaris superior and n. subcoeruleus) it significantly decreased, especially in WP animals. MAO B activity was reduced in the brain structures of WP rats, but activated or unchanged in EP rats. In all the structures studied the MAO B activity was significantly higher in EP, as compared to WP animals (f.e. in astrocytes: 0.314 +/- 0.012 and 0.200 +/- 0.012 units accordingly, p < 0.001). Despite the significant differences in the degree and direction of the changes in the activity of the MAO forms in rats with different alcohol craving, the calculated share of MAO A in the total MAO activity was regularly increased in all structures studied both in EP and WP animals; the share of MAO B activity accordingly decreased. CONCLUSIONS: Chronic alcohol consumption induces the great disturbances in brain MAO activity and isozyme composition following chronic ethanol consumption, strongly depending of the alcohol craving of the animals. It indicates the involvement of the enzyme in the mechanisms of central alcohol action.

Alcoholism↗
PubMed1997

Alcohol action on liver: dose dependence and morpho-biochemical correlations.

BACKGROUND: Since the duration and the dose of alcohol administration are acknowledged as factors that influence the risk of liver injury, it was interesting to compare the character and degree of liver damage following various doses and methods of alcohol administration. In addition, it was assumed to compare the degree of liver damage histologically and on the activity of marker liver enzymes in blood plasma in the same animals. METHODS AND RESULTS: The several experiments on heterogeneous stock rats with the various daily dose, duration and method of alcohol administration have been carried out. It was found, that the 9-month intake of 15.20% (v/v) ethanol solution as the only source of drinking (the consumption of absolute alcohol was about 4 g/kg/day) did not affect the normal development of animals and did not induce any harmful morphological changes in liver. Moreover, the liver parenchyma looks even better in the context of lesser inflammatory infiltration and vacuolisation of hypatocytes. The activities of the marker liver injury enzymes: alanine and aspartate amino transferases (ALT and AST), alkaline phosphatase (AP) as well as alcohol dehydrogenase (ADH) in blood were also not changed. The intragastric administration 25% (v/v) ethanol (3.5 g/kg twice a day, during 14 days) induced some morphological disturbances in the liver: an extension of blood capillaries and veins in parenchyma and insignificant increasing of the hepatocyte vacuolisation degree (from 0.7 +/- 0.1 points in control to 1.2 +/- 0.2 points in alcohol treated animals). In blood serum, a slight elevation of ADH (from 1.2 +/- 0.2 microM/min/l in control to 1.7 +/- 0.3) and AP (from 236 +/- 19 microM/min/l in control to 278 +/- 25) activities were found. The liquid alcohol diets (mean consumption of absolute alcohol was 14-18 g/kg/day, during a month) induced the more pronounced liver injury: extension of the liver blood vessels, inflammatory infiltration (from 1.1 +/- 0.1 points in control to 2.0 +/- 0.3; P, 0.05) and destruction of hepatocytes (from 0.5 +/- 0.01 points in control to 1.2 +/- 0.1; p < 0.05). Another liquid alcohol diet (mean consumption of absolute alcohol was 20-24 g/kg/day, during a month) induced the expressive hepatocyte vacuolisation (from 0.5 +/- 0.1 points in control to 1.5 +/- 0.2; p < 0.05). In both the experiments, the weaker staining of hepatocyte cytoplasms, basophilia in particular, were found. The activity of blood plasma ADH was insignificantly increased by 47% and 134% and that of AP--by 15% and 38%. The activity of ALT insignificantly increased in the third experiment only and AST remained unchanged. Some correlations among the morphological and biochemical indexes were found in the above experiments: between the degree of hepatocytes vacuolisation and the blood ADH or AP activities (r = 0.62; p < 0.01 and r = 0.54; p < 0.05), accordingly. The oxyphilia intensity correlated with the AST activity (r = 0.64; p < 0.01) and the intensity of hepatocyte basophilia with the ADH activity (r = 0.67; p < 0.01). The negative correlation was also found between the degree of extension of liver blood vessels and the activity of AST (r = -0.57; p < 0.05). CONCLUSIONS: The data obtained confirm the earlier observations concerning the dependence of the degree of liver injury on the dose and manner of alcohol administration as well as great individuality in the liver response to alcohol in heterogeneous stock rats. There are the significant correlations between the some morphological and biochemical markers of alcohol liver injury; among the biochemical markers studied, the ADH activity was the most sensitive.

Animals↗
PubMed1996

Distribution of catalase in rat brain: aminergic neurons as possible targets for ethanol effects.

Ethanol is metabolized at a slow but measurable rate in rodent brain. Recent studies indicate that this process is mediated mainly by catalase. The spatial distribution of this enzyme in different brain structures is poorly known. To explore possible local imbalances between the production and elimination of ethanol-derived acetaldehyde, we investigated the regional and cellular distribution of catalase, histo- and immunohistochemically, using serial cryostat sections from male Wistar rats. Compared to the strong peroxisomal staining seen in liver, brain catalase staining was weak and was not immunologically detected with an anti-sheep bovine catalase antibody. Activity was observed only in microperoxisomes, mainly in perikaryons of aminergic neurons, in the known groups of adrenergic, nonadrenergic and serotonergic neurons of the brain stem. Little peroxisomal staining was seen in other types of brain structures. This result contrasted to that of aldehyde dehydrogenase, which we previously observed to be widely distributed in brain structures, but with low activity in perikaryons of aminergic (especially catecholaminergic) neurons, as compared to cholinergic neurons. Our data indicate that catalase-mediated oxidation of ethanol to acetaldehyde takes place mainly in aminergic neurons, which seem to have a limited capacity for the subsequent removal via aldehyde dehydrogenase. This suggests that locally produced acetaldehyde could mediate CNS effects of ethanol in these structures.

Acetaldehyde↗
PubMed1996

Thiamine deficiency as predisposition to, and consequence of, increased alcohol consumption.

It was found that the activity of the marker thiamine-dependent enzyme, transketolase (TK), was decreased (down to 61-79% of control) in blood, liver and brain of inbred rats following a 6-month consumption of 15% ethanol as their only source of drinking fluid. After ethanol withdrawal, the enzyme activity was gradually restored, but did not reach the control values until 1 month following cessation of alcohol consumption. Moreover, in rats preferring ethanol, the decrease of TK activity was more pronounced than in water-preferring rats. Another experiment showed that thiamine deficiency induced by the thiamine antagonist, oxythiamine (200 mg/kg), led to a prolonged increase of the preferential intake of ethanol solutions in inbred rats. Significantly lower liver TK activities and thiamine pyrophosphate content were found in Finnish AA line rats as opposed to ANA line rats which had been obtained by selective outbreeding for high and low voluntary alcohol intake, respectively. Significantly lower TK activity was also found in the whole brain (89%), cerebellum (79%) and pons-medulla oblongata (87%) of AA rats as compared to ANA animals. Our own findings and the literature data confirm the hypothesis that thiamine deficiency can be both predisposing to and a consequence of, increased alcohol consumption.

Alcoholism↗
PubMed1995

Aldehyde dehydrogenase activities in the brains of rats and mice genetically selected for different sensitivity to alcohol.

Aldehyde dehydrogenase activity in brain has been studied for many years. However, the question of its role in the actions of ethanol in the brain has not been resolved. We have utilized mice and rats selectively bred for sensitivity or resistance to the initial hypnotic effects of ethanol to gain some insight into the possible involvement of brain aldehyde dehydrogenase in the actions of ethanol. We compared the levels of aldehyde dehydrogenase activity in the brains of these selected lines of rodents by histochemical methods. It was found that, although aldehyde dehydrogenase activity was detected in many areas of the brain, only in the cerebellar Purkinje cells was there a difference between sensitive and resistant lines of mice or rats. The resistant lines (Short Sleep mice and Low Alcohol Sensitive rats) had statistically higher levels of aldehyde dehydrogenase than did the sensitive lines (Long Sleep mice and High Alcohol Sensitive rats). Although this does not prove that aldehyde dehydrogenase or aldehydes are involved in the central actions of ethanol, it provides another piece of evidence in this direction.

Alcoholic Intoxication↗
PubMed1994

[Immunoenzyme and immunohistochemical analysis of class III alcohol dehydrogenase from human testis].

An enzyme-linked immunosorbent assay on the basis antialcohol dehydrogenase III (ADH III) monospecific antiserum has been devised. The immunoreactive protein content determined in two samples of human testis autopsy material was 1,288 and 1,047 mg/g of wet weight. ADH III has been revealed in all types of human testicular cells with the maximal content in spermatocytes and spermatogonia.

Alcohol Dehydrogenase↗
PubMed1992

Regional distribution of low-Km mitochondrial aldehyde dehydrogenase in the rat central nervous system.

To clarify the regional capacity of the brain to oxidize biogenic aldehydes and ethanol-derived acetaldehyde, a quantitative immunohistochemical study of the microregional and cellular expression of low Km mitochondrial aldehyde dehydrogenase (mALDH; EC 1.2.1.3) in the rat central nervous system was undertaken, using antiserum raised in rabbit against low-Km aldehyde dehydrogenase purified from rat liver mitochondria. mALDH-specific immunoreactivity (IR) was observed to various extent in the majority of structures in all brain and spinal cord areas. Staining was strong in the extranuclear cytoplasm of neuronal and glial cell bodies but less pronounced in their processes and terminals, the conducting tracts, white matter and neuropile and in blood vessels. Immunostaining density was 2 to 3 times higher in neuronal perikarya as compared with neuropile. mALDH-positive neurons were found in all brain regions, being strongest in the inferior olive and hippocampus stratum pyramidale and weakest in substantia nigra. The percentage of morphologically identifiable ALDH-positive neurons ranged from 40% in the arcuate hypothalamic nucleus to 88% in the cerebellar Purkinje cells. A comparison of the heterogeneous expression of mALDH in various rat CNS regions and cells, as observed in the present study, with the corresponding previously published distributions of the potential acetaldehyde-producing enzymes ADH and cytochrome P450 2E1 indicates major differences, which may help in understanding potential acetaldehyde-mediated CNS effects of ethanol. Knowledge of the regional distribution of high-affinity aldehyde dehydrogenase should also throw light on the neurophysiological role of local regulation of the metabolism of biogenic aldehydes in the brain.

Aldehyde Dehydrogenase↗
PubMed1991

Histochemical study of aldehyde dehydrogenase in the rat CNS.

A quantitative histochemical method was developed to determine aldehyde dehydrogenase (EC 1.2.1.3; ALDH) activity in the CNS. The distribution of ALDH activity in all rat brain and spinal cord regions is described. Among the CNS neuron structures, high enzyme activity was found in receptor and effector neurons, whereas low activity was noted in perikarya of the majority of intermediate neurons, including all aminergic neurons. A positive correlation was demonstrated between the distribution of ALDH activity among rat CNS microregions (our own data) and the density of dopaminergic terminals, dopamine content, and monoamine oxidase activity (literature data) among the same microregions. They may reflect a spatial linkage between ALDH and the predicted sites of natural aldehyde production. Lower enzyme activity was found in phylogenetically younger brain structures. It may explain the differential resistance of CNS structures to ethanol (acetaldehyde). Among the barrier CNS structures, moderate ALDH activity was found in capillaries and surrounding astrocytes and high activity was noted in ependimocytes covering the brain cavities and those of the vascular plexus. This provides realization of the function of ALDH as a brain metabolic barrier for aldehydes.

Acetaldehyde↗
PubMed1989

[Structural changes in the rat cerebral cortex induced by alcohol in combination with aldehyde dehydrogenase inhibitors].

The cerebral parietal cortex in rats subjected to an acute (single) and subacute (for 5 days) ethanol effect in combination with aldehyde dehydrogenase (AldDG) (enzymes classification 1.2.1.3 AldDG) inhibitors--disulfiram and cyanamide--has been investigated histochemically and electron microscopically. The inhibitors mentioned produce an essential decrease of AldDG activity in the cerebral cortex; it remains in some structures even 6 days after their single administration. Against the background of AldDG inhibitors alcohol produces more noticeable structural disorders in the cerebral cortex, they are possibly connected with accumulation of a highly toxic ethanol metabolite-acetaldehyde--in blood and with its easy penetration into the brain. This demonstrates an important role of AldDG in protection of the brain from alcoholic (aldehydic) lesions, as well as a peculiar danger for the brain of ethanol in combination with inhibitors of this enzyme.

Aldehyde Dehydrogenase↗