The Effect of Ethanol and Khat (Catha Edulis Forsk) on the Cerebellar Cortex of Early Postnatal Rats (original) (raw)
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Ethanol consumption has been linked with social and medical problems, coupled with damage of multiple organs including the cerebellum. The present study is aimed at investigating the histological and biochemical changes in the cerebellum of Wistar rats associated with ethanol exposure. The experimental animals were grouped into five groups designated as Group 1 which served as the control group and was given distilled water, Groups 2,3,4 and 5were given 40%, 25%, 12% and 5% v/v of ethanol respectively. Each of the experimental animals was administered 10mls/kg body weight of the stock solution for 42days after which the animals were sacrificed humanely. The cerebellum was removed, fixed in Bouins fluid for histological study while brain homogenates were prepared and used for the biochemical studies. Data was analyzed using one-way ANOVA and Tukey HSD Post-Hoc comparison test was used to determine where the difference lies. Oxidative stress studies showed significant increase and decrease in some oxidative stress markers when compared to the control group (p<0.05). The sialic acid studies showed a dose dependent decrease in the mean sialic acid concentration of the cerebellum across the groups when compared to the control (p<0.05). The histological studies showed the following changes; necrotic Purkinje cells with reduced linear distribution of Purkinje cells, in section of the cerebellar tissue of rats in Groups 2 and 3 with sections from Groups 4 and 5 remaining relatively normal when compared to the slide from the control group. Exposure to ethanol from the present studies showed a dose dependent effect on the cerebellum, as manifested in the histological and biochemical studies.
Effects of Lifelong Ethanol Consumption on Cerebellar Layer Volumes in AA and ANA Rats
Alcoholism: Clinical and Experimental Research, 1997
Aging and chronic alcohol consumption can cause degenerative changes in the cerebellar cortex. In this study, the effects of aging and lifelong alcohol consumption on cerebellar cortical layer volumes (molecular and granular) and also white matter layer volumes were studied in alcohol-preferring (AA) and nonpreferring (ANA) rats of both sexes. The ethanol-consuming animals (EtOH) had 12% (wlv) ethanol as the only available fluid from 4 to 22 months of age, whereas the young (3 month) and old controls (24 months) had only water to drink. The volumes of molecular, granular, and white matter layers of the cerebellar vermis in folia II, IV, VII, and X were measured by using systematic sampling and a point-counting method. The volumes of the granular and white matter layers showed consistent increase between 3 and 24 months of age, whereas the volume of the molecular layer remained unchanged with increasing age. Individual ethanol intake was measured over a 1-week period at the beginning and at the end of chronic ethanol exposure. Significant (ANOVA, p = 0.0oO) sex difference was found in the drinking behavior in both lines, with females consuming more alcohol than males (daily ethanol consumption at 22 months of age 3.2 f 0.3 vs. 7.1 f 0.3 glkg for AA males and females; 3.2 f 0.3 vs. 5.4 f 0.4 glkg for ANA males and females, respectively). The only ethanol-induced effect on the cerebellum was observed in ANA-EtOH females with a 15% reduction in the volumes of the molecular and granular layer in folium II compared with agematched controls and a significant ( p c 0.05, analysis of covariance with ethanol intake as a covariate) line difference in folium II (molecular and granular layers) was observed between ANA-EtOH females and AA-EtOH females. Furthermore, the volume of the molecular layer in folium II was significantly ( p c 0.05, analysis of covariance with ethanol intake and body weights as covariates) reduced for ANA-EtOH females, compared with ANA-EtOH males indicating a sex difference in the cerebellar degeneration due to chronic alcohol consumption. Of the three layers studied, the white matter layer was the most resistant layer to the effects caused by chronic alcohol consumption. In view of the fact that AA and ANA rats of both sexes differ regarding the drinking behavior and ethanol metabolism, they provide an important model for further research on ethanol-induced pathological changes in the central nervous system.
Alcoholism: Clinical and Experimental Research, 1998
The purpose of this study was to investigate the spontaneous activity of mature rat cerebellar neurons that had been exposed to ethanol (EtOH) during postnatal days 4 to 10, which corresponds to the third trimester in humans. Newborn Sprague-Dawley rats were implanted with gastric feeding tubes and were artificially reared from postnatal days 4 to 10 with two different diets. The experimental group received 4.5 g/kg/day of EtOH delivered in a milk solution. Controls received similar feeding with an isocaloric supplement replacing the EtOH. Electrophysiological evaluations were performed after an EtOH-free rearing period. Although lobules IX and X of the cerebellar vermis appeared morphologically smaller in the animals neonatally exposed to EtOH, compared with controls, extracellular recordings from both Purkinje cells and Golgi interneurons in adult rats showed no differences in spontaneous activity or firing pattern between the control and EtOH-exposed animals. Similarly, excitations and inhibitions of Purkinje neuron activity evoked by parallel pathway stimulation appeared unaffected by the developmental EtOH exposure. However, we did observe a significant decrease in the proportion of Purkinje neurons generating complex spike bursts in the group exposed to EtOH neonatally. These data suggest that, although fewer Purkinje neurons may survive the brain growth spurt if exposed to EtOH during this critical period of development, those that do survive appear to function normally. The observed abnormality in complex spike production may result from EtOH effects on developing neurons in the inferior olive that give rise to the climbing fibers that cause this bursting pattern in Purkinje neurons.
Distribution and Kinetics of Ethanol Metabolism in Rat Brain
Alcoholism: Clinical and Experimental Research, 1998
It was found that the accumulation of acetaldehyde produced from 50 rnM ethanol in rat brain homogenates takes place in all major brain regions. The velocity varied between 3.5 to 7.1 nmoVmg of proteidhr. 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-l,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.
International Journal of Developmental Neuroscience, 2005
Migration of the external granular layer cells in the cerebellum of rats was delayed after exposure to moderate levels of ethanol during a pre-gestational period, through gestation and lactation until weaning. After ethanol withdrawal, cell soma and dendrites were observed to be larger in granule cells. Likewise, Bergmann glia showed several cytoarchitectonic features suggesting cell immaturity, as well as some apparent compensatory plastic responses after ethanol withdrawal. These effects may be due to ethanol impairing neurotrophin-mediated processes during cerebellar development that could lead to alterations in Purkinje cell structure and activity, and thereafter in the psychoneural functions in which the cerebellar cortex is involved.
Experimental Neurology, 1977
Ethanol was applied directly to cultures of mouse cerebellum and cerebral neocortex while spontaneous electrical activity was monitored in the former and stimulus-elicited responses were monitored in the latter. Ethanol characteristically demonstrated an initial excitatory effect on cerebellar cultures, 1 Ethanol determinations were performed in the Drug Assay Laboratory, Stanford University, through the courtesy of Drs.
The effect of acute and chronic exposure to ethanol on the developing encephalon: a review
2008
Objectives: to compare the acute and chronic effects of ethanol on the neural development, by analysis of the ontogenetic neural structure of mammals. Methods: searches were performed in the following electronic databases: MEDLINE, SciElo, PubMed, LILACS, CAPES periodical, and the Open Journal System. The descriptors used were: "chronic ethanol toxicity", "chronic alcohol toxicity", "acute ethanol toxicity", "acute alcohol", "neural ontogenic development", "neuronal migration disturbances", "neural structure". The following inclusion criteria were used: articles published between 2003 and 2007, some classic articles in the field and an important neuropsychology textbook. Results: the analysis of papers revealed that, although several studies of the chronic effects of ethanol exposure on the mammalian nervous system have been conducted, only a few have investigated the acute effects of ethanol on specific days of gestation, and these studies have revealed important disorders relating to the cerebral tissue. Conclusions: it should be recommended that women refrain from the consumption of ethanol during gestational phase to protect the fetus' health. Furthermore, the acute consumption of ethanol by women nearing the eighth or ninth week of gestation has been shown to be potentially harmful to the nervous tissue of the fetus.
Ethanol-induced neuroapoptosis in the developing rodent cerebellum and related brain stem structures
Developmental Brain Research, 2005
For three decades since the fetal alcohol syndrome (FAS) was first described, researchers have been keenly interested in understanding the mechanism(s) by which ethanol damages or disrupts development of the human fetal brain. It has been reported repeatedly that exposure of infant rats to ethanol causes a reduction in brain mass and loss of cerebellar Purkinje cells, but the mechanisms underlying these effects have remained elusive. In a recent series of studies, we have demonstrated that exposure of infant rats or mice to ethanol on a single occasion during the synaptogenesis period of development causes neurons in many regions of the developing central nervous system to commit suicide (die by apoptosis), but the cerebellum was not among the brain regions focused upon in these studies. Here we show in infant rats and mice that one-time exposure to ethanol triggers acute neurodegeneration of Purkinje cells and other neurons in the cerebellar cortex, deep cerebellar nuclei, and two related brainstem nuclei (nucleus pontis, inferior olivary complex). We also describe the time course of neurodegeneration and window of vulnerability for each of these neuronal cell types and demonstrate that the cell death process in each case is unequivocally apoptotic. We conclude that exposure of infant rats or mice to ethanol on a single occasion during synaptogenesis can kill Purkinje cells, and many other neuronal populations at all levels of the developing neuraxis, and in each case the mechanism of cell death is apoptosis. D