Neurofunctional effects of developmental alcohol exposure in alcohol-preferring and alcohol-nonpreferring rats.
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The neurofunctional effects of developmental alcohol exposure (3% v/v solution from day 15 of gestation to day 7 after parturition) have been investigated in Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rat lines, selectively bred for opposite alcohol preference and consumption. Alcohol exposure significantly decreased the rate of ultrasonic emission in sP male pups; whereas, it did not affect this indicator of emotional reactivity in sNP animals. Perinatal alcohol intake did not influence either learning of an active avoidance task or hippocampal long-term potentiation in both offspring lines. Significant differences in time spent exploring novel objects were observed between control sP and sNP rats subjected to the novel exploration object test. Alcohol exposed sP rats, but not alcohol exposed sNP rats, apparently lost the capacity to discriminate between the novel and the familiar object, even though this difference is difficult to interpret because of the large differences in the respective responses to the novel objects. Neurochemical experiments have shown that basal levels of dopamine (DA) and homovanillic acid (HVA) were significantly higher in the nucleus accumbens (NAC) of sP rats with respect to sNP animals. Perinatal alcohol did not affect basal DA and HVA concentrations or amphetamine-induced DA increase and HVA decrease in the NAC of either sP or sNP offspring. These results suggest that subtle behavioral alterations induced by developmental exposure to low doses of alcohol, which do not cause malformations and/or overt neurotoxicity, may be associated with genetic factors, although not necessarily those responsible for differences in alcohol preference. (+info)
Attributable risk of common and rare determinants of subarachnoid hemorrhage.
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BACKGROUND AND PURPOSE: Smoking, hypertension, alcohol consumption, autosomal dominant polycystic kidney disease (ADPKD), and positive family history for subarachnoid hemorrhage (SAH) are well-known risk factors for SAH. For effective prevention, knowledge about the contribution of these risk factors to the overall occurrence of SAH in the general population is pivotal. We therefore investigated the population attributable risks of the risk factors for SAH. METHODS: We retrieved the relative risk and prevalence of established risk factors for SAH from the literature and calculated the population attributable risks of these risk factors. RESULTS: Drinking alcohol 100 to 299 g/wk accounted for 11% of the cases of SAH, drinking alcohol >/=300 g/wk accounted for 21%, and smoking accounted for 20%. An additional 17% of the cases could be attributed to hypertension, 11% to a positive family history for SAH, and 0.3% to ADPKD. CONCLUSIONS: Screening and preventive treatment of patients with familial preponderance of SAH alone will cause a modest reduction of the incidence of SAH in the general population. Further reduction can be achieved by reducing the prevalence of the modifiable risk factors alcohol consumption, smoking, and hypertension. (+info)
Mechanisms of alcohol-induced damage to the developing nervous system.
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Numerous mechanisms likely contribute to the damaging effects of prenatal alcohol exposure on the developing fetus and particularly the developing central nervous system (CNS). The coexistence of a multitude of mechanisms that may act simultaneously or consecutively and differ among various cell types poses particular challenges to researchers. To study alcohol's effects on the fetus more easily, investigators have used animal models and tissue-culture experiments. Such approaches have identified numerous potential mechanisms through which alcohol acts on the fetus, many of which result in cell death by necrosis or apoptosis. Among these mechanisms are increased oxidative stress, damage to the mitochondria, interference with the activity of growth factors, effects on glia cells, impaired development and function of chemical messenger systems involved in neuronal communication, changes in the transport and uptake of the sugar glucose, effects on cell adhesion, and changes in the regulation of gene activity during development. (+info)
Teratogenic effects of alcohol on brain and behavior.
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Children prenatally exposed to alcohol can suffer from serious cognitive deficits and behavioral problems as well as from alcohol-related changes in brain structure. Neuropsychological studies have identified deficits in learning and memory as well as in executive functioning both in children with fetal alcohol syndrome and in children with less severe impairments. Both groups of children also exhibit problem behaviors, such as alcohol and drug use, hyperactivity, impulsivity, and poor socialization and communication skills. Brain imaging studies have identified structural changes in various brain regions of these children--including the basal ganglia, corpus callosum, cerebellum, and hippocampus--that may account for the cognitive deficits. Functional brain imaging studies also have detected changes in alcohol-exposed children indicative of deficits in information processing and memory tasks. (+info)
A 47-year-old alcoholic man with progressive abnormal gait.
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Central pontine myelinolysis should be considered in the differential diagnosis of a patient with a history of alcoholism and malnutrition presenting with ataxia, regardless of serum sodium values. T2-weighted images are the most sensitive imaging technique, but changes may not be evident for weeks after the insult, and in addition, the insult may not be known. Supportive care is important to prevent complications, but no treatment has been found to be effective in treating the illness. Patient outcomes vary considerably and are difficult to predict. (+info)
Ethanol-induced apoptosis in the developing visual system during synaptogenesis.
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PURPOSE: Ethanol is known to have deleterious effects on the human fetal nervous system (fetal alcohol syndrome), including components of the visual system, but only modest progress has been made in understanding these effects. The authors have recently demonstrated that, during the period of synaptogenesis, a single episode of ethanol intoxication lasting for several hours triggers a massive wave of apoptotic neurodegeneration in several regions of the developing rat or mouse forebrain. The present study was undertaken to determine to what extent the developing visual system is vulnerable to the apoptogenic effects of ethanol. METHODS: Infant rats and mice at ages from birth to 21 days were treated subcutaneously with a single dose of ethanol or with two doses, 2 hours apart, on a single day. Blood alcohol levels were determined, and the retinas and visual centers in the brain were examined by light and electronmicroscopy at various times from 4 to 24 hours after treatment. RESULTS: Retinal ganglion cells and neurons in the lateral geniculate nucleus, superior colliculus, and visual cortex were all highly susceptible to ethanol's apoptogenic action, the period of peak sensitivity being postnatal days 1 to 4 for ganglion cells and 4 to 7 for the other visual neurons. A transient elevation of blood alcohol to approximately 120 mg/dL was sufficient to activate the cell death program in visual neurons. CONCLUSIONS: During synaptogenesis, a single ethanol intoxication episode triggers apoptotic cell death of neurons at all levels of the visual system from retina to the visual cortex. (+info)
Signaling cascades regulating NMDA receptor sensitivity to ethanol.
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One of the major targets for ethanol (alcohol) in the brain is the N-methyl-D-aspartate (NMDA) receptor, a glutamate-gated ion channel. Intriguingly, the effects of ethanol on the NMDA receptor are not homogeneous throughout the brain. This review focuses on recent studies revealing molecular mechanisms that mediate the actions of ethanol on the NMDA receptor in different brain regions via changes in NMDA receptor phosphorylation and compartmentalization. Specifically, the role of the scaffolding protein RACK1 and the regulatory protein DARPP-32 in mediating the distinct effects of ethanol is presented. (+info)
Temporally specific burst in cell proliferation increases hippocampal neurogenesis in protracted abstinence from alcohol.
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Adult neurogenesis is a newly considered form of plasticity that could contribute to brain dysfunction in psychiatric disease. Chronic alcoholism, a disease affecting over 8% of the adult population, produces cognitive impairments and decreased brain volumes, both of which are partially reversed during abstinence. Clinical data and animal models implicate the hippocampus, a region important in learning and memory. In a model of alcohol dependence (chronic binge exposure for 4 d), we show that adult neurogenesis is inhibited during dependence with a pronounced increase in new hippocampal neuron formation after weeks of abstinence. This increase is attributable to a temporally and regionally specific fourfold increase in cell proliferation at day 7 of abstinence, with a majority of those cells surviving and differentiating at percentages similar to controls, effects that doubled the formation of new neurons. Although increases in cell proliferation correlated with alcohol withdrawal severity, proliferation remained increased when diazepam (10 mg/kg) was used to reduce withdrawal severity. Indeed, those animals with little withdrawal activity still show a twofold burst in cell proliferation at day 7 of abstinence. Thus, alcohol dependence and recovery from dependence continues to alter hippocampal plasticity during abstinence. Because neurogenesis may contribute to hippocampal function and/or learning, memory, and mood, compensatory neurogenesis and the return of normal neurogenesis may also have an impact on hippocampal structure and function. For the first time, these data provide a neurobiological mechanism that may underlie the return of human cognitive function and brain volume associated with recovery from addiction. (+info)