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Acute maternal ethanl (alcohol) administration induces different craniofacial anomalies in the offspring of experimental animals, depending on the gestational day of teratogen exposure. Previous studies in our laboratories have illustrated the sequence of developmental changes leading to the "typical" fetal alcohol syndrome (FAS) craniofacial phenotype which results from teratogen exposure during gastrulation. These facial features are accompanied by deficiencies in median forebrain derivatives. Ethanol teratogenesis at this time apparently results in a loss of midline territory of the embryonic disc with little effects on neural crest-dependent laterally derived structures including the visceral arches. Acute ethanol exposure in mice 1 1/2 days later, at a time when neural crest cells are populating the frontonasal prominence and the visceral arches, results in a craniofacial phenotype that is similar to that noted in the DiGeorge anomaly or sequence. Sequential scanning electron microscopic analysis in our laboratory of embryos exposed on day 8 1/2 have illustrated deficiencies in the developing facial prominences and the visceral arches. The developing forebrain and midbrain appear hypoplastic. We have also observed heart, great vessel, and thymus abnormalities in these fetuses. Histologic analyses indicate that a common pathogenetic basis for the above-mentioned (day 8 1/2-induced) fetal alcohol effects appears to be an interference with the integrity of the cranial (including occipital) neural crest. Other discrete cell populations may also be involved since we have observed abnormalities in other regions, including placodal and closing membrane tissues. This animal model provides evidence linking maternal ethanol abuse during the 3rd or 4th weeks of human gestation to the development in the conceptus of FAS or DiGeorge anomally craniofacial characteristics, respectively. As the DiGeorge anomaly has been noted in the offspring of alcoholic women, this animal model indicates that ethanol and/or its metabolites is, in these cases, the causative agent.

Alcohol abuse and dependence remain significant public health issues, and yet the brain circuits that are involved in the rewarding effects of alcohol are poorly understood. One promising way to study the effects of alcohol on neural activity is to examine its effects on functional connectivity between brain areas involved in reward and other functions. Here, we compared the effects of two doses of alcohol (0.4 and 0.8 g/kg) to placebo on resting-state functional connectivity in brain circuits related to reward in 19 healthy young men without histories of alcohol problems. The higher, but not the lower, dose of alcohol, significantly increased connectivity from reward-related regions to sensory and motor cortex, and between seeds associated with cognitive control. Contrary to expectation, alcohol did not significantly change connectivity for the ventral striatum at either dose. These findings reveal unrecognized effects of alcohol on connectivity from reward-related regions to visual and sensory cortical areas.

In 2010, the Municipality of Cuenca, through its environmental management commission (EMC), and the World Bank, through the environment and natural resources department, started a collaboration targeted towards strengthening EMC’s capacity to better manage Cuenca’s environmental assets and to provide EMC with hard evidence and data that will serve as departing point for decision-makers towards the formulation of public policy. Two main areas of focus were chosen: (i) costs of environmental degradation for Cuenca; and (ii) climate change impacts and resilience measures for Cuenca. This report describes the findings of the first area of focus. This report tries to capture the main results and to describe the assumptions and input data utilized, through a detailed step-by-step description of an internationally-accepted and validated methodology, an explanation of input data needs, equations used, assumptions made, and alternative calculation streams; and through the demonstration of this methodology as it is applied to the real case of air pollution in Cuenca. Analyses about the cost of environmental degradation are often used as an environmental priority-setting tool, because it gives the estimated socio-economic costs of environmental degradation (air pollution, inadequate water supply, sanitation, hygiene, and others). In this report, the methodology was used only for air pollution; similar studies can be replicated for other areas in order to have a full description of the different sources of pollution and the subsequent costs that Cuenca is subject to. Economic analysis (cost-benefit analysis) can be applied as a useful tool to prioritize among these interventions options with respect to their efficiency and cost effectiveness. Some policy reforms may also require to understand the political economy of reforms, for example, when taxi technology or bus technology of private firms is to be changed.

We investigated the effect of pretreatment with a prostaglandin synthetase inhibitor, ibuprofen, on the pharmacokinetics and pharmacodynamics of ethanol in six fasting subjects. Ibuprofen caused a 10% decrease in the maximum rate of elimination of ethanol. Visual memory, which is a function primarily mediated by the right cerebral hemisphere, was measured by the Benton Visual Retention test and was more impaired during combined ibuprofen and ethanol dosing than during ethanol dosing alone (P = 0.05). The auditory-verbal memory of the subjects, which is primarily a function of the left cerebral hemisphere, was assessed by the Selective Reminding Test and showed decreased impairment during combined ibuprofen and ethanol dosing as compared with ethanol dosing alone (P = 0.04). The opposite effect of ibuprofen on ethanol-induced cognitive impairment as measured by two lateralized functions is consistent with the reports in tissue and animal models that central nervous system effects of ethanol may be mediated at least in part by prostaglandins.

Microglia undergo maturation during the third trimester of human development (equivalent to the first 1-2 weeks of postnatal life in rodents), during which these cells may be particularly sensitive to insult. Alcohol exposure during this period can activate the neuroimmune system, an effect that may contribute to the pathophysiology of fetal alcohol spectrum disorders. Here, we investigated whether repeated alcohol exposure during the third trimester-equivalent in rats has a priming effect on the neuroimmune response to injection of bacterial lipopolysaccharide (LPS). Pups were exposed to alcohol in vapor chambers for 4 h daily from postnatal day (PD)2 to PD16 (peak blood alcohol concentrations ∼150 mg/dL). On PD17, rats were injected with either saline or LPS (50 μg/kg) and the frontal cortex, cerebellar vermis, and dentate gyrus were collected 2 h later. Messenger RNA (mRNA) levels for the pro-inflammatory agents interleukin 1β (IL-1β) and chemokine (C-C) motif ligand 2 (CCL2), as well as levels of the anti-inflammatory cytokine interleukin 10 (IL-10), were measured using reverse transcriptase polymerase chain reaction. LPS consistently increased IL-1β and CCL2 mRNA levels in the dentate gyrus, frontal cortex, and cerebellum of both male and female rats. Furthermore, the LPS-induced increase of IL-1β mRNA levels was significantly blunted in the frontal cortex of alcohol-exposed female rats. Conversely, LPS only minimally affected IL-10 mRNA expression and there were no significant differences between air- and alcohol-exposed rats. Taken together with the literature regarding the effect of third-trimester alcohol exposure on the neuroimmune system, our findings suggest that chronic exposure to lower levels is less disruptive to the neuroimmune system than binge-like exposure to high doses of alcohol.

Abstract When acetyl ethyl tetramethyl tetralin (AETT), at 10–50 μg/ml, was added to rat liver mitochondria respiring with succinate or with glutamate plus malate as substrate, the rate of mitochondrial respiration increased significantly after an initial lag period, of 2–3 min. AETT also stimulated respiration in the presence of oligomycin, and at higher concentrations of AETT a phase of strongly inhibited respiration followed an initial stimulatory phase. These observations suggest that AETT uncouples oxidative phosphorylation. A diketo derivative (DK) of tetramethyl tetralin also appears to be an uncoupling agent, according to those criteria, and both compounds uncoupled mitochondria from brain as well as liver. DK and many other uncoupling agents, such as hexachlorophene (HCP), produced an immediate burst of respiration, whereas the brief lag after addition of AETT was similar to that seen after addition of triethyltin (TET).

Background and ObjectivesThe study examined the effects of an alcohol challenge on naturalistic drinking among alcohol‐dependent individuals and explored brief motivational interviewing (MI) as a potential intervention for these participants.MethodAlcohol‐dependent individuals (n = 32, eight females) completed the intake assessment, alcohol challenge, one MI session, and 1‐month follow‐up (87.5% retention) where they completed measures of drinking and motivation for change.ResultsAs expected, multilevel mixed models revealed that drinking did not increase post‐alcohol challenge. Participants reported a reduction in ambivalence, drinking days, and a trend towards fewer total drinks between the MI and 1‐month follow‐up.ConclusionsConsistent with other studies, the alcohol challenge did not worsen alcohol use. Results support further investigation of brief MI for alcohol‐dependent participants in alcohol challenges.Scientific SignificanceAlcohol administration to alcohol‐dependent participants appears to not exacerbate naturalistic drinking. MI may be a feasible intervention for non‐treatment seeking alcohol‐dependent participants in alcohol challenge studies. (Am J Addict 2014;23:96–101)

Background: Short‐sleep (SS) mice exhibit higher locomotor activity than do long‐sleep (LS) mice when injected with low doses of ethanol or the noncompetitive N‐methyl‐D‐aspartate receptor (NMDAR) antagonist MK‐801 (dizocilpine). SS mice also have higher densities of brain NMDARs. However, two strains of LS X SS recombinant inbred (RI) mice also show differential activation to ethanol and MK‐801, but have similar numbers of NMDARs. Here we used inbred LS (ILS) and SS (ISS) mice to investigate further the relationship between NMDARs and sensitivity to the stimulant effects of low doses of ethanol.Methods: Open field activity and spontaneous alternations were measured after saline or drug injection. [3H]MK‐801 binding parameters were determined in hippocampus, cortex, striatum, and nucleus accumbens. Extracellular field excitatory postsynaptic potentials (fEPSPs) were recorded in the CA1 region of hippocampal slices.Results: Systemic injection of either ethanol or MK‐801 increased locomotor activity to a greater extent in ISS mice than in ILS mice. The competitive NMDAR antagonist 2‐carboxypiperazin‐4‐yl‐propyl‐1–1phosphonic acid (±CPP) depressed activity of ILS, but not ISS, mice. No strain differences were observed in spontaneous alternations or in the number or affinity of NMDARs in the brain regions examined. Likewise, the magnitudes of hippocampal NMDAR‐mediated fEPSPs were similar in ILS and ISS mice and were inhibited to the same extent by a competitive NMDAR antagonist. However, both ethanol and the NMDAR NR2B receptor antagonist ifenprodil inhibited the late component of hippocampal NMDAR fEPSPs to a greater extent in ISS, than in ILS, mice.Conclusions: Differential ethanol‐ and MK‐801‐induced behavioral activation in ILS and ISS mice was not associated with differences in NMDAR number. Nonetheless, pharmacological differences in hippocampal NMDAR responsiveness suggest that ISS mice express NMDARs that have a greater sensitivity to noncompetitive, but not competitive, NMDAR antagonists. These differences, which may reflect differences in NMDAR subunit composition, could underlie the differential responsiveness to low doses of ethanol in ILS and ISS mice.