Influence of vitamin E, sodium selenite, and astrocyte-conditioned medium on neuronal survival after chronic exposure to ethanol.

Free radicals species generation during ethanol metabolism is implicated in ethanol-induced toxicity. Findings from clinical studies have clearly established the association between alcohol intake and nutritional deficiency. Astrocytes are able to promote neuronal survival against different lethal injuries involved in ethanol-induced toxicity. We therefore studied the ability of hydrosoluble vitamin E (trolox), sodium selenite, and astrocyte-conditioned medium to protect cultured rat neurones against ethanol-induced oxidative stress after chronic exposure to ethanol. When a 6-day exposure to ethanol (20 mM) led to a loss of cell viability, the presence of trolox (10 microM) offered a significant neuroprotection. In the presence of 3-amino-1,2,4-triazole, a catalase inhibitor that created conditions that were favorable to reactive oxygen species accumulation, trolox was able to counteract the deleterious effect of the inhibitor. Moreover, flow cytometric analysis indicated that trolox can maintain the intracellular glutathione content in neurones chronically exposed to ethanol. In these conditions of exposure, the absence of sodium selenite in the culture medium significantly aggravated the exposure-induced effects, whereas sodium selenite (100 nM) offered a significant neuroprotection. Finally, the presence of 25% astrocyte-conditioned medium in the neuronal culture medium induced a neuroprotective effect in the presence of ethanol. Nevertheless, when astrocytes were previously chronically (3 days) exposed to ethanol, their culture medium did not offer a significant protection. These results evidenced that vitamin E and astrocytes can protect neurones from ethanol-induced oxidative stress, notably by contributing to maintaining the intracellular glutathione levels. Selenium, by means of its exogenous addition in the form of sodium selenite, also had an interesting neuroprotective effect.     

Neonatal alcohol exposure produces more severe motor coordination deficits in high alcohol sensitive rats compared to low alcohol sensitive rats.

Prenatal exposure to alcohol can produce a number of behavioral alterations, including hyperactivity, learning deficits and motor impairments. However, the severity and nature of behavioral alterations varies markedly among children of women who drink during pregnancy. One important determinant of this variation may be genetic differences in the response to alcohol. Recently, we demonstrated that exposure to alcohol during development produced hyperactivity in rats bred for high alcohol sensitivity (HAS), but not in rats bred for low alcohol sensitivity (LAS). These lines were selectively bred for extremes in alcohol-induced "sleep time." The present study investigated the effects of ethanol exposure during development on motor coordination later in life in both HAS and LAS rats. Using an artificial rearing procedure, neonatal pups from each line were exposed to a binge-like alcohol treatment on postnatal days (PD) 4-9. Within each line, one group was exposed to ethanol (6.0 g/kg/day), one group served as an artificially reared control, and a third served as a normally reared control group. On PD 30, parallel bar motor performance was evaluated. Exposure to ethanol during development severely impaired motor performance in the HAS rats compared to their controls. In LAS rats, early ethanol exposure produced only mild and nonsignificant effects on motor performance. Thus, HAS rats were more vulnerable to ethanol-induced motor deficits compared to the LAS rats. Importantly, there were no differences in peak blood alcohol level between the lines, indicating that vulnerability to ethanol's teratogenic effects was not due to differences in metabolic rate. These results suggest that genetic differences in response to alcohol may serve as a predictor for susceptibility to ethanol's teratogenic effects.     

Organ growth and cellular development in ethanol-exposed rats

Effects of perinatal exposure to ethanol on growth and cellular development were investigated. Alcohol was administered in liquid diets designed to provide optimal nutrition during pregnancy. Pair-fed and ad lib control groups were included. The 3 groups of females were similar in body weight during gestation and lactation, and offspring weights were similar on gestation Day 21 and at birth. By Day 9 of lactation control pups weighted more than both alcohol and pair-fed pups which were similar in body weight. Weights of brain, heart, liver and kidney were reduced in alcohol pups compared to pair-feds and controls. Decreased liver weight reflected both decreased cell size and decreased protein content, but was primarily due to decreased caloric intake. Decreased heart weight appeared to result from a direct effect of ethanol on heart protein content. Even more marked were the adverse effects of ethanol on kidney protein content and kidney DNA (reflecting a decrease in cell number). In contrast, although both absolute brain weight and DNA content were decreased in ethanol-exposed offspring, relative brain weight was increased. Finally, maternal ethanol consumption significantly increased relative placenta weights as well as placental DNA and protein content.     

Alcohol intake during prenatal life affects neuroimmune mediators and brain neurogenesis

Several lines of evidence suggest that alcohol exposure during prenatal gestation, or during early postnatal life may be a risk factor for the manifestation of neurological and for immune-related disorders in later life. The cellular, biochemical and molecular mechanisms of ethanol toxicity, however, have not been yet clearly established. Recent studies indicated that neurotrophin signaling pathways may be involved in ethanol mediated cell death. The present investigation addressed the question of whether nerve growth factor (NGF), which is the first and best characterized member of the neurotrophin family, and NGF-target cells are affected by prenatal exposure to alcohol. The result of our study indicates that NGF synthesis and the functional activity of NGF-target cells localized in the brain are markedly influenced by ethanol intake. The possible link between such changes and the hypothesis that these alterations may contribute to certain of the neuropathology observed following alcohol exposure would be discussed.     

An in vitro model for studying the effects of continuous ethanol exposure on N-methyl-d-aspartate receptor function

Long-term ethanol exposure has deleterious effects on both glial and neuronal function. We assessed alterations in both astrocytic and neuronal viability, and alterations in N-methyl-d-aspartate receptor (NMDAR) function, in cocultures of rat cerebellar granule cells (CGCs) and astrocytes after continuous ethanol exposure (CEE). Treatment of cells with 100 mM EtOH once every 24 h for 4 days resulted in a mean ethanol concentration of 57.3 ± 2.1 mM. Comparisons between control and post-ethanol-treated cells were made 4 days after the last ethanol treatment. CEE did not alter glial cell viability, as indicated by the absence of either changes in astrocytic morphology, actin depolymerization, or disruption of astrocytic intracellular mitochondrial distribution at any day postethanol treatment. The CGCs were healthy and viable after CEE, as indicated by phase-contrast microscopy and the trypan-blue exclusion method. Whole-cell patch-clamp experiments indicated that NMDA-induced currents (I_NMDA) were altered by CEE treatment. Similar to previous results obtained during the withdrawal phase from chronic ethanol exposure, I_NMDA from CEE-treated cells were significantly larger than I_NMDA from NMDARs in control CGCs, but returned to control values by the fourth day post-CEE. However, after the last ethanol dosing and during a time when ethanol concentrations remained high, I_NMDA were significantly smaller than control values. Identical results were observed in CGCs expressing the NR2A or NR2B subunit. In summary, both neurons and astrocytes remained healthy following exposure to CEE with no signs of neurotoxicity at the cellular level, and modulation of NMDAR function is consistent with findings from prior experiments. Thus, we conclude that the CEE paradigm in glial-neuronal cocultures readily lends itself to long-term in vitro studies of ethanol effects that include glial-neuronal interactions and the ability to study ethanol withdrawal-induced neurotoxicity.     

Chronic consumption of ethanol leads to substantial cell damage in cultured rat astrocytes in conditions promoting acetaldehyde accumulation

AIMS: This study aimed at comparing the cerebral cytotoxicity of ethanol and its main metabolite acetaldehyde after acute or chronic exposures of rat astrocytes in primary culture. METHODS: Cytotoxicity was evaluated on the cell reduction of viability (MTT reduction test) and on the characterization of DNA damage by single cell gel electrophoresis (or comet assay). RESULTS: Changes in astrocyte survival and in DNA integrity only occurred when the astrocytes were chronically exposed to ethanol (20 mM; 3, 6 or 9 days). On the other hand, viability and DNA integrity were deeply affected by acute exposure to acetaldehyde. Both effects were dependent on the concentration of acetaldehyde. The cytotoxic effect of acetaldehyde was also indirectly evaluated after modifications of the normal ethanol metabolism by the use of different inducers or inhibitors. In presence of ethanol, the concomitant induction of catalase (i.e. by glucose oxidase) and inhibition of aldehyde dehydrogenase (i.e. by methylene blue) led to acetaldehyde accumulation within cells. It was followed by both a reduction in viability and a substantial increase in DNA strand breaks. CONCLUSIONS: These data were thus consistent with a possible predominant role of acetaldehyde during brain ethanol metabolism. On the other hand, the effects observed after AMT could also suggest a possible direct ethanol effect and a role for free radical attacks. These data were thus consistent with a possible predominant role of acetaldehyde during brain ethanol metabolism. On the other hand, the effects observed after AMT could also suggest a possible direct ethanol effect and a role for free radical attacks.     

Adolescent ethanol exposure: does it produce long-lasting electrophysiological effects?

This review discusses evidence for long-lasting neurophysiological changes that may occur following exposure to ethanol during adolescent development in animal models. Adolescence is the time that most individuals first experience ethanol exposure, and binge drinking is not uncommon during adolescence. If alcohol exposure is neurotoxic to the developing brain during adolescence, not unlike it is during fetal development, then understanding how ethanol affects the developing adolescent brain becomes a major public health issue. Adolescence is a critical time period when cognitive, emotional, and social maturation occurs and it is likely that ethanol exposure may affect these complex processes. To study the effects of ethanol on adolescent brain, animal models where the dose and time of exposure can be carefully controlled that closely mimic the human condition are needed. The studies reviewed provide evidence that demonstrates that relatively brief exposure to high levels of ethanol, via ethanol vapors, during a period corresponding to parts of adolescence in the rat is sufficient to cause long-lasting changes in functional brain activity. Disturbances in waking electroencephalogram and a reduction in the P3 component of the event-related potential (ERP) have been demonstrated in adult rats that were exposed to ethanol vapor during adolescence. Adolescent ethanol exposure was also found to produce long-lasting reductions in the mean duration of slow-wave sleep (SWS) episodes and the total amount of time spent in SWS, a finding consistent with a premature aging of sleep. Further studies are necessary to confirm these findings, in a range of strains, and to link those findings to the neuroanatomical and neurochemical mechanisms potentially underlying the lasting effects of adolescent ethanol exposure.     

Glycosylation is altered by ethanol in rat hippocampal cultured neurons

AIMS: Glycoproteins, such as adhesion molecules and growth factors, participate in the regulation of nervous system development. Ethanol affects the synthesis, intracellular transport, distribution, and secretion of N-glycoproteins in different cell types, including astrocytes and hepatocytes, suggesting alterations in the glycosylation process. We analysed the effect of exposure to low doses of ethanol (30 mm, 7 days) on glycosylation in cultured hippocampal neurons. METHODS: Neurons were incubated for short (5 min) and long (90 min) periods with the radioactively labelled carbohydrate precursors 2-deoxy-glucose, N-acetyl-D-mannosamine and mannose. The uptake and metabolism of these precursors, as well as the radioactivity distribution in protein gels, were analysed. The levels of the glucose transporters GLUT1 and GLUT3 were also determined. RESULTS: Ethanol exposure reduces the synthesis of proteins, DNA and RNA and decreased the uptake of mannose, but not of 2-deoxy-glucose and N-acetyl-D-mannosamine, and it increased the protein levels of both glucose transporters. Moreover, it altered the carbohydrate moiety of several proteins. Finally, alcohol treatment results in an increment of cell surface glycoconjugates containing terminal non-reduced mannose. CONCLUSIONS: Alcohol-induced alterations in glycosylation of proteins in neurons could be a key mechanism involved in the teratogenic effects of alcohol exposure on brain development.     

Effects of periadolescent ethanol exposure on alcohol preference in two BALB substrains.

Ethanol exposure during adolescence is a rite of passage in many societies, but only a subset of individuals exposed to ethanol becomes dependent on alcohol. To explore individual differences in response to ethanol exposure, we compared the effects of periadolescent ethanol exposure on alcohol drinking in an animal model. Male and female mice of two BALB substrains were exposed to ethanol in one of three forms--choice [water vs. 10% (volume/volume) ethanol], forced (10% ethanol in a single bottle), or gradual (single bottle exposure, starting with 0.5% ethanol and increasing at 2-day intervals to 10% ethanol)--from the 6th through the 12th week of age and administered two-bottle alcohol preference tests (10% ethanol vs. water) for 15 days immediately thereafter. All three forms of ethanol exposure increased alcohol preference in male and female BALB/cByJ mice, relative to findings for ethanol-naive control animals. Only gradual ethanol exposure produced an increase in alcohol preference in BALB/cJ mice. During extended alcohol preference testing (for a total of 39 days) of mice in the gradual ethanol exposure group, the higher alcohol preference of the gradual ethanol-exposed BALB/cByJ male mice persisted, but alcohol preference of control group female mice in this strain--formerly ethanol naive, but at this point having received 10% ethanol in the two-bottle paradigm for 15 days--rose to the level of alcohol preference of female mice in the gradual ethanol exposure group. This finding demonstrated that both adolescent and adult ethanol exposure stimulated alcohol preference in female mice of this strain. Across days of testing in adulthood, alcohol preference of the gradual ethanol-exposed BALB/cJ mice decreased, resulting in a lack of effect of gradual exposure to ethanol on alcohol preference in both male and female mice of this strain during the period of extended testing. These strain differences support a genetic basis for the effects of ethanol exposure on alcohol preference and fit within a body of literature, showing substantial individual differences in the effects of ethanol exposure among genetically undefined rats and differences in response to ethanol exposure among inbred rat strains. Exploration of the mechanisms underlying this gene by environment interaction in a mouse model may help elucidate individual differences in the effects of ethanol exposure in human beings and contribute to the understanding of the causes of alcoholism.     

Chronic ethanol exposure leads to divergent control of dopaminergic synapses in distinct target regions

Neuroadaptations following chronic exposure to alcohol are hypothesized to play important roles in alcohol-induced alterations in behavior, in particular increased alcohol drinking and anxiety like behavior. Dopaminergic signaling plays a key role in reward-related behavior, with evidence suggesting it undergoes modification following exposure to drugs of abuse. A large literature indicates an involvement of dopaminergic signaling in response to alcohol. Using a chronic inhalation model of ethanol exposure in mice, we have begun to investigate the effects of alcohol intake on dopaminergic signaling by examining protein levels of tyrosine hydroxylase and the dopamine transporter, as well as monoamine metabolites in three different target fields of three different dopaminergic nuclei. We have focused on the dorsal lateral bed nucleus of the stria terminalis because of the reported involvement of dorsal lateral bed nucleus of the stria terminalis dopamine in ethanol intake, and the nucleus accumbens and dorsal striatum because of their dense dopaminergic innervation. After either a chronic intermittent exposure or continuous exposure regimen, mice were killed, and tissue punches collected from the dorsal lateral bed nucleus of the stria terminalis, nucleus accumbens, and striatum for Western analysis. Strikingly, we found divergent regulation of tyrosine hydroxylase and dopamine transporter protein levels across these three regions that was dependent upon the means of exposure. These data thus suggest that distinct populations of catecholamine neurons may be differentially regulated by ethanol, and that ethanol and withdrawal interact to produce differential adaptations in these systems.     

Influence of prenatal ethanol exposure on vascular contractile response in rat thoracic aorta.

Fetal alcohol syndrome is associated with cardiovascular malformation. However, the impact of prenatal ethanol exposure on vascular function is not clear. The purpose of this study was to examine the influence of prenatal ethanol exposure on vascular response in adulthood. Timed-pregnancy, female rats were fed an ethanol-containing liquid diet (36% calorically or 6.36% [vol./vol.]) or control diet from gestation day 2 until labor. The pups continued to receive a standard rat chow through adulthood, and the force-generating capacity of aortic ring segments was examined. Prenatal ethanol exposure did not significantly affect postnatal growth, but it did lead to elevated blood pressure in adulthood. The contractile response to potassium chloride was similar in vessels with intact endothelium, although the median effective concentration (EC(50)) was significantly reduced by prenatal ethanol exposure in rings with denuded endothelium. The response to norepinephrine was attenuated by prenatal ethanol exposure in rings with either intact or denuded endothelium. The endothelium-dependent relaxation to carbamylcholine chloride was significantly attenuated by prenatal ethanol exposure. Vasorelaxant response to the nitric oxide donor sodium nitroprusside or beta-adrenergic agonist isoproterenol was similar between control and prenatal-ethanol-exposed groups with either intact or denuded endothelium. Ethanol elicited a dose-dependent endothelium-dependent vasorelaxation, which was comparable between the two animal groups. The ethanol-induced endothelium-dependent vasorelaxation was attenuated by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester. These findings seem to indicate that prenatal ethanol exposure contributes to alterations of both endothelium-dependent and endothelium-independent vascular contractile responses.     

Ethanol exposure of neonatal rats does not increase biomarkers of oxidative stress in isolated cerebellar granule neurons.

Oxidative stress is a candidate mechanism for ethanol neuropathology in fetal alcohol spectrum disorders. Oxidative stress often involves production of reactive oxygen species (ROS), deterioration of the mitochondrial membrane potential (MMP), and cell death. Previous studies have produced conflicting results regarding the role of oxidative stress and the benefit of antioxidants in ethanol neuropathology in the developing brain. This study investigated the hypothesis that ethanol neurotoxicity involves production of ROS with negative downstream consequences for MMP and neuron survival. This was modeled in neonatal rats at postnatal day 4 (P4) and P14. It is well established that granule neurons in the rat cerebellar cortex are more vulnerable to ethanol neurotoxicity on P4 than at later ages. Thus, it was hypothesized that ethanol produces more oxidative stress and its negative consequences on P4 than on P14. A novel experimental approach was used in which ethanol was administered to animals in vivo (gavage 6g/kg), granule neurons were isolated 2-24h post-treatment, and ROS production and relative MMP were immediately assessed in the viable cells. Cells were also placed in culture and survival was measured 24h later. The results revealed that ethanol did not induce granule cells to produce ROS, cause deterioration of neuronal MMP, or cause neuron death when compared to vehicle controls. Further, granule neurons from neither P4 nor P14 animals mounted an oxidative response to ethanol. These findings do not support the hypothesis that oxidative stress is obligate to granule neuron death after ethanol exposure in the neonatal rat brain. Other investigators have reached a similar conclusion using either brain homogenates or cell cultures. In this context, it is likely that oxidative stress is not the sole and perhaps not the principal mechanism of ethanol neurotoxicity for cerebellar granule neurons during this stage of brain development.     

Neuromotor effects of acute ethanol inhalation exposure in humans: a preliminary study

Ethanol (ETOH) is added to unleaded gasoline to decrease environmental levels of carbon monoxide from automobiles emissions. Therefore, addition of ETOH in reformulated fuel will most likely increase and the involuntarily human exposure to this chemical will also increase. This preliminary study was undertaken to evaluate the possible neuromotor effects resulting from acute ETOH exposure by inhalation in humans. Five healthy non-smoking adult males, with no history of alcohol abuse, were exposed by inhalation, in a dynamic, controlled-environment exposure chamber, to various concentrations of ETOH (0, 250, 500 and 1,000 ppm in air) for six hours. Reaction time, body sway, hand tremor and rapid alternating movements were measured before and after each exposure session by using the CATSYS 7.0 system and a diadochokinesimeter. The concentrations of ETOH in blood and in alveolar air were also measured. ETOH was not detected in blood nor in alveolar air when volunteers were exposed to 250 and 500 ppm, but at the end of exposure to 1,000 ppm, blood and alveolar air concentrations were 0.443 mg/100ml and 253.1 ppm, respectively. The neuromotor tests did not show conclusively significant differences between the exposed and non-exposed conditions. In conclusion, this study suggests that acute exposure to ethanol at 1,000 ppm or lower or to concentrations that could be encountered upon refueling is not likely to cause any significant neuromotor alterations in healthy males.     

Changes in brain microvasculature resulting from early postnatal alcohol exposure

The microvasculature in selected brain regions in rats was examined on postnatal day 10 following exposure to alcohol on postnatal days 4 to 10. The alcohol-exposed rats were artificially reared and given 6.6 g/kg of ethanol condensed into 8 hr of each 24-hr period. A gastrostomy-control group was reared in the same manner but maltose-dextrin was substituted for ethanol in the formula. A suckle-control group was reared normally by dams. Measurements were taken from midsagittal sections of the cerebellum and sections of the hippocampal formation at a midtemporal level. Although the overall area of the vermal cerebellum was decreased as a consequence of the alcohol exposure, the capillary density was unchanged. However, cerebellar capillary diameters were increased in some lobules in the alcohol-exposed rats. In the dentate gyrus, there was a trend toward a decrease in capillary numerical density but no change in regional area or capillary diameter in the alcohol-exposed rats. In the hippocampus proper, there was a decrease in regional area, no change in capillary density, and an increase in capillary diameter due to alcohol. These results indicate that alcohol exposure during the early postnatal period affects the microvasculature differentially in the cerebellum, hippocampus proper and dentate gyrus.     

Ethanol exposure alters the development of serotonergic neurons in chick spinal cord

Exposure to ethanol is known to alter the development of the serotonergic system. However, previous studies have examined large populations of cells and have not determined the effects of ethanol on individual serotonergic neurons. In the present study, the effects of various concentrations of ethanol on the development of single serotonergic neurons in the chick embryo spinal cord were determined using immunohistochemical techniques. Between embryonic day 7 (E7) and E14, ethanol administrations produced in ovo alcohol concentrations of: a) low dose, 30–60 mg/dl, b) medium dose, 150–200 mg/dl, or c) high dose, 240–300 mg/dl. In animals exposed to the medium and high ethanol doses, the normal developmental increase in cross-sectional area of the somata was not observed. At all stages examined, the numbers of primary and nonprimary processes were significantly lower in ethanol-treated groups compared to controls. These data indicate that ethanol exposure induces dose-dependent alterations in the development of identified spinal cord neurons. The ethanol-induced changes may be involved in the motor dysfunction observed after embryonic ethanol exposure.     

THE EFFECTS OF CHRONIC ALCOHOL CONSUMPTION ON PREGNANT RATS AND THEIR OFFSPRING

The effect of chronic ethanol intake during gestation was studiedin rats fed a liquid diet in which ethanol provided 36% of thetotal calories. The animals were chronically alcoholised beforemating, and the body weight gain and nutritional status duringpregnancy were noted. Blood ethanol levels were measured duringpregnancy and parturition. Specifically, we have shown thatchronic ethanol intake during pregnancy lengthens the gestationperiod, decreases foetal viability, increases the placentalweight and diminishes foetus, liver and brain weights, as wellas the protein and DNA content of foetal brain. The reducedbody weight of rats prenatally exposed to alcohol continuedfor the first two months of the postnatal period and was mostapparent during lactation.     

Metabolic effects of ethanol on primary cell cultures of rat skeletal muscle.

Individuals who have consumed alcohol chronically accumulate glycogen in their skeletal muscles. Changes in the energy balance caused by alcohol consumption might lead to alcoholic myopathy. Experimental models used in the past, such as with skeletal muscle biopsy samples of alcohol-dependent individuals or in animal models, do not distinguish between direct effects and indirect effects (i.e., alterations to the nervous or endocrine system) of alcohol. In the current study, we evaluated the direct effect of ethanol on skeletal muscle glycogen concentrations and related glycolytic pathways. We measured the changes in metabolite concentrations and enzyme activities of carbohydrate metabolism in primary cell cultures of rat skeletal muscle exposed to ethanol for two periods. The concentrations of glycolytic metabolites and the activities of several enzymes that regulate glucose and glycogen metabolism were measured. After a short exposure to ethanol (6 h), glucose metabolism slowed. After 48 h of exposure, glycogen accumulation was observed.     

Ethanol exposure during the early first trimester equivalent impairs reflexive motor activity and heightens fearfulness in an avian model

Prenatal alcohol exposure is a leading cause of childhood neurodevelopmental disability. The adverse behavioral effects of alcohol exposure during the second and third trimester are well documented; less clear is whether early first trimester-equivalent exposures also alter behavior. We investigated this question using an established chick model of alcohol exposure. In ovo embryos experienced a single, acute ethanol exposure that spanned gastrulation through neuroectoderm induction and early brain patterning (19-22 h incubation). At 7 days posthatch, the chicks were evaluated for reflexive motor function (wingflap extension, righting reflex), fearfulness (tonic immobility [TI]), and fear/social reinstatement (open-field behavior). Chicks exposed to a peak ethanol level of 0.23-0.28% were compared against untreated and saline-treated controls. Birds receiving early ethanol exposure had a normal righting reflex and a significantly reduced wingflap extension in response to a sudden descent. The ethanol-treated chicks also displayed heightened fearfulness, reflected in increased frequency of TI, and they required significantly fewer trials for its induction. In an open-field test, ethanol treatment did not affect latency to move, steps taken, vocalizations, defecations, or escape attempts. The current findings demonstrate that early ethanol exposure can increase fearfulness and impair aspects of motor function. Importantly, the observed dysfunctions resulted from an acute ethanol exposure during the period when the major brain components are induced and patterned. The equivalent period in human development is 3-4 weeks postconception. The current findings emphasize that ethanol exposure during the early first trimester equivalent can produce neurodevelopmental disability in the offspring.     

Prenatal exposure to alcohol in rat: effect on intestinal enzymes in offspring

Intestinal hydrolase activities were studied during postnatal development in the offspring of rats exposed to 20% ethanol during gestation; alcohol was withdrawn at birth. Controls received water during gestation. Sucrase, lactase, glucoamylase and aminopeptidase activities were determined 2 and 4 weeks after birth in the proximal jejunum. Offspring prenatally exposed to ethanol showed a deficit in body weight and lower aminopeptidase activity during the suckling period (2 weeks). These effects were reversible by 4 weeks when alcohol was withdrawn at birth. The prenatal exposure to ethanol did not change the pattern of sucrase maturation in the intestine of offsprings. The activities of lactase and glucoamylase were not modified following prenatal exposure to ethanol. In conclusion, exposure to ethanol during gestation caused decreased abilities for the intestine of the offspring to digest protein.