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Sample records for alcohol exposure induced

  1. Potential role of adolescent alcohol exposure-induced amygdaloid histone modifications in anxiety and alcohol intake during adulthood.

    PubMed

    Pandey, Subhash C; Sakharkar, Amul J; Tang, Lei; Zhang, Huaibo

    2015-10-01

    Binge drinking is common during adolescence and can lead to the development of psychiatric disorders, including alcoholism in adulthood. Here, the role and persistent effects of histone modifications during adolescent intermittent ethanol (AIE) exposure in the development of anxiety and alcoholism in adulthood were investigated. Rats received intermittent ethanol exposure during post-natal days 28-41, and anxiety-like behaviors were measured after 1 and 24 h of the last AIE. The effects of AIE on anxiety-like and alcohol-drinking behaviors in adulthood were measured with or without treatment with the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA). Amygdaloid brain regions were collected to measure HDAC activity, global and gene-specific histone H3 acetylation, expression of brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated (Arc) protein and dendritic spine density (DSD). Adolescent rats displayed anxiety-like behaviors after 24 h, but not 1 h, of last AIE with a concomitant increase in nuclear and cytosolic amygdaloid HDAC activity and HDAC2 and HDAC4 levels leading to deficits in histone (H3-K9) acetylation in the central (CeA) and medial (MeA), but not in basolateral nucleus of amygdala (BLA). Interestingly, some of AIE-induced epigenetic changes such as, increased nuclear HDAC activity, HDAC2 expression, and decreased global histone acetylation persisted in adulthood. In addition, AIE decreased BDNF exons I and IV and Arc promoter specific histone H3 acetylation that was associated with decreased BDNF, Arc expression and DSD in the CeA and MeA during adulthood. AIE also induced anxiety-like behaviors and enhanced ethanol intake in adulthood, which was attenuated by TSA treatment via normalization of deficits in histone H3 acetylation of BDNF and Arc genes. These novel results indicate that AIE induces long-lasting effects on histone modifications and deficits in synaptic events in the amygdala, which are

  2. Early Maternal Deprivation Enhances Voluntary Alcohol Intake Induced by Exposure to Stressful Events Later in Life

    PubMed Central

    Peñasco, Sara; Mela, Virginia; López-Moreno, Jose Antonio; Viveros, María-Paz; Marco, Eva M.

    2015-01-01

    In the present study, we aimed to assess the impact of early life stress, in the form of early maternal deprivation (MD, 24 h on postnatal day, pnd, 9), on voluntary alcohol intake in adolescent male and female Wistar rats. During adolescence, from pnd 28 to pnd 50, voluntary ethanol intake (20%, v/v) was investigated using the two-bottle free choice paradigm. To better understand the relationship between stress and alcohol consumption, voluntary alcohol intake was also evaluated following additional stressful events later in life, that is, a week of alcohol cessation and a week of alcohol cessation combined with exposure to restraint stress. Female animals consumed more alcohol than males only after a second episode of alcohol cessation combined with restraint stress. MD did not affect baseline voluntary alcohol intake but increased voluntary alcohol intake after stress exposure, indicating that MD may render animals more vulnerable to the effects of stress on alcohol intake. During adolescence, when animals had free access to alcohol, MD animals showed lower body weight gain but a higher growth rate than control animals. Moreover, the higher growth rate was accompanied by a decrease in food intake, suggesting an altered metabolic regulation in MD animals that may interact with alcohol intake. PMID:25821601

  3. Acanthoic Acid Can Partially Prevent Alcohol Exposure-Induced Liver Lipid Deposition and Inflammation.

    PubMed

    Yao, You-Li; Han, Xin; Li, Zhi-Man; Lian, Li-Hua; Nan, Ji-Xing; Wu, Yan-Ling

    2017-01-01

    Aims: The present study aims to detect the effect of acanthoic acid (AA) on alcohol exposure-induced liver lipid deposition and inflammation, and to explore the mechanisms. Methods: C57BL/6 mice were pretreated with single dose of AA (20 and 40 mg/kg) by oral gavage or equal volume of saline, and then exposed to three doses of ethanol (5 g/kg body weight, 25%, w/v) by gavage within 24 h. The mice were sacrificed at 6 h after the last ethanol dosing. Serum and hepatic indexes were detected by western blot, RT-PCR, and histopathological assay. AML-12 cells were pretreated with AA (5, 10, 20 μM), or AICAR (500 μM), GW3965 (1 μM), SRT1720 (6 μM), Nicotinamide (20 mM) for 2 h, respectively, and then following treated with EtOH (200 mM) and lipopolysaccharide (LPS) (10 ng/ml) for additional 48 h. Cell protein and mRNA were collected for western blot and RT-PCR. Cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) release were detected by ELISA assay. Results: It was found that AA significantly decreased acute ethanol-induced increasing of the serum ALT/AST, LDH, ALP levels, and hepatic and serum triglyceride levels, and reduced fat droplets accumulation in mice liver. AA significantly suppressed the levels of sterol regulatory element binding protein 1 (SREBP-1), cytochrome P4502E1 (CYP2E1), IL-1β, and caspase-1 induced by ethanol. Furthermore, a significant decline of sirtuin 1 (Sirt1) and liver X receptors (LXRs) levels was observed in EtOH group, compared with normal group mice. And AA pretreatment increased the Sirt1 and LXRs levels, and also ameliorated phosphorylation of liver kinase B-1 (LKB-1), adenosine monophosphate-activated protein kinase (AMPK), acetyl CoA carboxylase (ACC) proteins, compared with EtOH group. However, the levels of peroxisome proliferator activated receptor -α or -γ (PPAR-α or PPAR-γ) induced by acute ethanol were reversed by AA. In EtOH/LPS cultivated AML-12 cells, AA decreased IL-1β and TNF-α levels, lipid

  4. Acanthoic Acid Can Partially Prevent Alcohol Exposure-Induced Liver Lipid Deposition and Inflammation

    PubMed Central

    Yao, You-Li; Han, Xin; Li, Zhi-Man; Lian, Li-Hua; Nan, Ji-Xing; Wu, Yan-Ling

    2017-01-01

    Aims: The present study aims to detect the effect of acanthoic acid (AA) on alcohol exposure-induced liver lipid deposition and inflammation, and to explore the mechanisms. Methods: C57BL/6 mice were pretreated with single dose of AA (20 and 40 mg/kg) by oral gavage or equal volume of saline, and then exposed to three doses of ethanol (5 g/kg body weight, 25%, w/v) by gavage within 24 h. The mice were sacrificed at 6 h after the last ethanol dosing. Serum and hepatic indexes were detected by western blot, RT-PCR, and histopathological assay. AML-12 cells were pretreated with AA (5, 10, 20 μM), or AICAR (500 μM), GW3965 (1 μM), SRT1720 (6 μM), Nicotinamide (20 mM) for 2 h, respectively, and then following treated with EtOH (200 mM) and lipopolysaccharide (LPS) (10 ng/ml) for additional 48 h. Cell protein and mRNA were collected for western blot and RT-PCR. Cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) release were detected by ELISA assay. Results: It was found that AA significantly decreased acute ethanol-induced increasing of the serum ALT/AST, LDH, ALP levels, and hepatic and serum triglyceride levels, and reduced fat droplets accumulation in mice liver. AA significantly suppressed the levels of sterol regulatory element binding protein 1 (SREBP-1), cytochrome P4502E1 (CYP2E1), IL-1β, and caspase-1 induced by ethanol. Furthermore, a significant decline of sirtuin 1 (Sirt1) and liver X receptors (LXRs) levels was observed in EtOH group, compared with normal group mice. And AA pretreatment increased the Sirt1 and LXRs levels, and also ameliorated phosphorylation of liver kinase B-1 (LKB-1), adenosine monophosphate-activated protein kinase (AMPK), acetyl CoA carboxylase (ACC) proteins, compared with EtOH group. However, the levels of peroxisome proliferator activated receptor -α or -γ (PPAR-α or PPAR-γ) induced by acute ethanol were reversed by AA. In EtOH/LPS cultivated AML-12 cells, AA decreased IL-1β and TNF-α levels, lipid

  5. Drunk bugs: Chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice.

    PubMed

    Peterson, Veronica L; Jury, Nicholas J; Cabrera-Rubio, Raúl; Draper, Lorraine A; Crispie, Fiona; Cotter, Paul D; Dinan, Timothy G; Holmes, Andrew; Cryan, John F

    2017-04-14

    The gut microbiota includes a community of bacteria that play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N=10) or air (Control, N=9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (p<0.05) and beta (p<0.001) diversity, with a notable decrease in alpha diversity in CIE. These results demonstrate that CIE exposure markedly alters the gut microbiota in mice. Significant increases in genus Alistipes (p<0.001) and significant reductions in genra Clostridium IV and XIVb (p<0.001), Dorea (p<0.01), and Coprococcus (p<0.01) were seen between CIE mice and Control. These findings support the viability of the CIE method for studies investigating the microbiota-gut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress.

  6. Alcohol-induced brain growth restrictions (microencephaly) were not affected by concurrent exposure to cocaine during the brain growth spurt.

    PubMed

    Chen, W J; Andersen, K H; West, J R

    1994-09-01

    The prevalence of concomitant use of alcohol and cocaine among drug abusers has raised concern about the possible increased risk of fetal damage. The aim of this study was to assess the interactive effects of alcohol and cocaine on lethality, somatic growth, and brain growth using an animal model system. Sprague-Dawley rat pups were used as subjects. They were randomly assigned to 1 of the 9 artificially reared groups which varied with respect to the combination treatments of cocaine (0, 40, or 60 mg/kg) and alcohol (0, 3.3, or 4.5 g/kg). All artificially reared pups were given daily cocaine and alcohol treatments during a major part of the brain growth spurt period (postnatal days 4-9). An additional group of suckled control animals raised by their natural dams was included to control for artificial rearing. The results are summarized as follows: 1) Drug-induced lethality was higher in cocaine-treated groups when compared with non-cocaine-treated groups, and the concurrent administration of high doses of alcohol and cocaine significantly increased the mortality rate. 2) Somatic growth, in terms of body weight, was not affected by alcohol, cocaine, or the combination of both drugs using the artificial rearing technique. 3) Alcohol exposure during this brain growth spurt period significantly reduced whole brain weight, as well as forebrain, cerebellum, and brain stem weights. 4) In contrast to alcohol, cocaine failed to exert a detrimental effect on brain weight measures during this early postnatal period.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. In Utero Exposure to Low-Dose Alcohol Induces Reprogramming of Mammary Development and Tumor Risk in MMTV-erbB-2 Transgenic Mice

    PubMed Central

    Ma, Zhikun; Blackwelder, Amanda J.; Lee, Harry; Zhao, Ming; Yang, Xiaohe

    2015-01-01

    There is increasing evidence that prenatal exposure to environmental factors may modify breast cancer risk later in life. This study aimed to investigate the effects of in utero exposure to low-dose alcohol on mammary development and tumor risk. Pregnant MMTV-erbB-2 mice were exposed to alcohol (6 g/kg/day) between day 13 and day 19 of gestation, and the female offspring were examined for tumor risk. Whole mount analysis indicated that in utero exposure to low-dose alcohol induced significant increases in ductal extension at 10 weeks of age. Molecular analysis showed that in utero alcohol exposure induced upregulation of ERα signaling and activation of Akt and Erk1/2 in pubertal mammary glands. However, enhanced signaling in the EGFR/erbB-2 pathway appeared to be more prominent in 10-week-old glands than did signaling in the other pathways. Interestingly, tumor development in mice with in utero exposure to low-dose alcohol was slightly delayed compared to control mice, but tumor multiplicity was increased. The results indicate that in utero exposure to low-dose alcohol induces the reprogramming of mammary development by mechanisms that include altered signaling in the estrogen receptor (ER) and erbB-2 pathways. The intriguing tumor development pattern might be related to alcohol dose and exposure conditions, and warrants further investigation. PMID:25853264

  8. Fetal Alcohol Exposure

    MedlinePlus

    ... of the National Academies (IOM) diagnostic categories: 4 » Fetal Alcohol Syndrome (FAS) » Partial FAS (pFAS) » Alcohol-Related Neurodevelopmental Disorder ( ... 301.443.3860 Relevant Clinical Diagnoses IOM Diagnoses Fetal Alcohol Syndrome (FAS) Fetal Alcohol Syndrome (FAS) was the first ...

  9. Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development

    PubMed Central

    Wang, G; Bieberich, E

    2010-01-01

    Fetal alcohol syndrome (FAS) is caused by maternal alcohol consumption during pregnancy. The reason why specific embryonic tissues are sensitive toward ethanol is not understood. We found that in neural crest-derived cell (NCC) cultures from the first branchial arch of E10 mouse embryos, incubation with ethanol increases the number of apoptotic cells by fivefold. Apoptotic cells stain intensely for ceramide, suggesting that ceramide-induced apoptosis mediates ethanol damage to NCCs. Apoptosis is reduced by incubation with CDP-choline (citicoline), a precursor for the conversion of ceramide to sphingomyelin. Consistent with NCC cultures, ethanol intubation of pregnant mice results in ceramide elevation and increased apoptosis of NCCs in vivo. Ethanol also increases the protein level of prostate apoptosis response 4 (PAR-4), a sensitizer to ceramide-induced apoptosis. Prenatal ethanol exposure is concurrent with malformation of parietal bones in 20% of embryos at day E18. Meninges, a tissue complex derived from NCCs, is disrupted and generates reduced levels of TGF-β1, a growth factor critical for bone and brain development. Ethanol-induced apoptosis of NCCs leading to defects in the meninges may explain the simultaneous presence of cranial bone malformation and cognitive retardation in FAS. In addition, our data suggest that treatment with CDP-choline may alleviate the tissue damage caused by alcohol. PMID:21364652

  10. Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development.

    PubMed

    Wang, G; Bieberich, E

    2010-05-27

    Fetal alcohol syndrome (FAS) is caused by maternal alcohol consumption during pregnancy. The reason why specific embryonic tissues are sensitive toward ethanol is not understood. We found that in neural crest-derived cell (NCC) cultures from the first branchial arch of E10 mouse embryos, incubation with ethanol increases the number of apoptotic cells by fivefold. Apoptotic cells stain intensely for ceramide, suggesting that ceramide-induced apoptosis mediates ethanol damage to NCCs. Apoptosis is reduced by incubation with CDP-choline (citicoline), a precursor for the conversion of ceramide to sphingomyelin. Consistent with NCC cultures, ethanol intubation of pregnant mice results in ceramide elevation and increased apoptosis of NCCs in vivo. Ethanol also increases the protein level of prostate apoptosis response 4 (PAR-4), a sensitizer to ceramide-induced apoptosis. Prenatal ethanol exposure is concurrent with malformation of parietal bones in 20% of embryos at day E18. Meninges, a tissue complex derived from NCCs, is disrupted and generates reduced levels of TGF-β1, a growth factor critical for bone and brain development. Ethanol-induced apoptosis of NCCs leading to defects in the meninges may explain the simultaneous presence of cranial bone malformation and cognitive retardation in FAS. In addition, our data suggest that treatment with CDP-choline may alleviate the tissue damage caused by alcohol.

  11. Moderate Level Prenatal Alcohol Exposure Induces Sex Differences in Dopamine D1 Receptor Binding in Adult Rhesus Monkeys

    PubMed Central

    Converse, Alexander K.; Moore, Colleen F.; Holden, James E.; Ahlers, Elizabeth O.; Moirano, Jeffrey M.; Larson, Julie A.; Resch, Leslie M.; DeJesus, Onofre T.; Barnhart, Todd E.; Nickles, Robert J.; Murali, Dhanabalan; Christian, Bradley T.; Schneider, Mary L.

    2014-01-01

    Background We examined the effects of moderate prenatal alcohol exposure and/or prenatal stress exposure on D1 receptor binding in a nonhuman primate model. The dopamine D1 receptor is involved in executive function, and it may play a role in cognitive behavioral deficits associated with prenatal alcohol and/or stress exposure. Little is known, however, about the effects of prenatal alcohol and/or stress exposure on the D1 receptor. We expected that prenatal insults would lead to alterations in D1 receptor binding in prefrontal cortex and striatum in adulthood. Methods Rhesus macaque females were randomly assigned to moderate alcohol exposure and/or mild prenatal stress as well as a control condition during pregnancy. Thirty eight offspring were raised identically and studied as adults by non-invasive in vivo neuroimaging using positron emission tomography (PET) with the D1 antagonist radiotracer [11C]SCH 23390. Radiotracer binding in prefrontal cortex and striatum was evaluated by 2 (alcohol) × 2 (stress) × 2 (sex) analysis of variance. Results In prefrontal cortex, a significant alcohol × sex interaction was observed with prenatal alcohol exposure leading to increased [11C]SCH 23390 binding in male monkeys. No main effect of prenatal alcohol or prenatal stress exposure was observed. Conclusions These results suggest that prenatal alcohol exposure results in long-term increases in prefrontal dopamine D1 receptor binding in males. This may help explain gender differences in the prevalence of neurodevelopmental disorders consequent to prenatal alcohol exposure. PMID:25581649

  12. Long-term cognitive, emotional and neurogenic alterations induced by alcohol and methamphetamine exposure in adolescent rats.

    PubMed

    Loxton, David; Canales, Juan J

    2017-03-06

    A high proportion of young methamphetamine (MA) users simultaneously consume alcohol. However, the potential neurological and behavioural alterations induced by such a drug combination have not been systematically examined. We studied in adolescent rats the long-term effects of alcohol, MA, and alcohol and MA combined on anxiety-like behaviour, memory, and neurogenesis in the adult hippocampus. Rats received saline, ethanol (ETOH, 1.5g/kg), MA (MA, 2mg/kg), or ethanol and MA combined (ETHOH-MA, 1.5g/kg ethanol plus 2mg/kg MA) via oral gavage, once daily for 5 consecutive days. Open field (OF), elevated plus maze (EPM) and radial arm maze (RAM) tests were conducted following a 15-day withdrawal period. The results showed alterations in exploratory behaviour in the OF in the MA and ETOH-MA groups, and anxiety-like effects in the EPM in all three drug treatment groups. All three drug groups exhibited reference memory deficits in the RAM, but only the combination treatment group displayed alterations in working memory. Both MA and ETOH-MA treatments increased the length of doublecortin (DCX)-void gaps in the dentate gyrus but only ETOH-MA treatment increased the number of such gaps. An increased number and length of DCX-void gaps correlated with decreased exploratory activity in the OF, and impaired working memory in the RAM was associated with an augmented number of gaps. These findings suggest that alterations in adult hippocampal neurogenesis are linked to the persistent cognitive and behavioural deficits produced by alcohol and MA exposure.

  13. Fetal alcohol exposure: consequences, diagnosis, and treatment.

    PubMed

    Pruett, Dawn; Waterman, Emily Hubbard; Caughey, Aaron B

    2013-01-01

    Maternal alcohol use during pregnancy is prevalent, with as many as 12% of pregnant women consuming alcohol. Alcohol intake may vary from an occasional drink, to weekly binge drinking, to chronic alcohol use throughout pregnancy. Whereas there are certain known consequences from fetal alcohol exposure, such as fetal alcohol syndrome, other effects are less well defined. Craniofacial dysmorphologies, abnormalities of organ systems, behavioral and intellectual deficits, and fetal death have all been attributed to maternal alcohol consumption. This review article considers the theoretical mechanisms of how alcohol affects the fetus, including the variable susceptibility to fetal alcohol exposure and the implications of ethanol dose and timing of exposure. Criteria for diagnosis of fetal alcohol syndrome are discussed, as well as new methods for early detection of maternal alcohol use and fetal alcohol exposure, such as the use of fatty acid ethyl esters. Finally, current and novel treatment strategies, both in utero and post utero, are reviewed.

  14. Prenatal exposure to vanilla or alcohol induces crawling after these odors in the neonate rat: The role of mu and kappa opioid receptor systems.

    PubMed

    Gaztañaga, Mirari; Aranda-Fernández, P Ezequiel; Chotro, M Gabriela

    2015-09-01

    Rat fetuses can perceive chemosensory stimuli derived from their mother's diet, and they may learn about those stimuli. In previous studies we have observed that prenatal exposure to alcohol during the last days of gestation increases the acceptance and liking of an alcohol flavor in infant and adolescent rats. While these results were not found after prenatal exposure to vanilla, cineole or anise, suggesting that the pharmacological properties of alcohol, mediated by the opioid system, underlie the effects observed with this drug. Considering that other studies report enhanced acceptance of non-alcohol flavors experienced prenatally when subjects were tested before infancy, we explore the possibility of observing similar results if testing 1-day old rats exposed prenatally to vanilla. Using an "odor-induced crawling" testing procedure, it was observed that neonates exposed prenatally to vanilla or alcohol crawl for a longer distance towards the experienced odor than to other odors or than control pups. Blocking mu, but not kappa opioid receptors, reduced the attraction of vanilla odor to neonates exposed to vanilla in utero, while the response to alcohol in pups exposed prenatally to this drug was affected by both antagonists. Results confirm that exposure to a non-alcohol odor enhances postnatal responses to it, observable soon after birth, while also suggesting that the mu opioid receptor system plays an important role in generating this effect. The results also imply that with alcohol exposure, the prenatal opioid system is wholly involved, which could explain the longer retention of the enhanced attraction to alcohol following prenatal experience with the drug.

  15. Paternal Alcohol Exposure Reduces Alcohol Drinking and Increases Behavioral Sensitivity to Alcohol Selectively in Male Offspring

    PubMed Central

    Finegersh, Andrey; Homanics, Gregg E.

    2014-01-01

    Alcohol use disorder (AUD) is heritable, but the genetic basis for this disease remains poorly understood. Although numerous gene variants have been associated with AUD, these variants account for only a small fraction of the total risk. The idea of inheritance of acquired characteristics, i.e. “epigenetic inheritance,” is re-emerging as a proven adjunct to traditional modes of genetic inheritance. We hypothesized that alcohol drinking and neurobiological sensitivity to alcohol are influenced by ancestral alcohol exposure. To test this hypothesis, we exposed male mice to chronic vapor ethanol or control conditions, mated them to ethanol-naïve females, and tested adult offspring for ethanol drinking, ethanol-induced behaviors, gene expression, and DNA methylation. We found that ethanol-sired male offspring had reduced ethanol preference and consumption, enhanced sensitivity to the anxiolytic and motor-enhancing effects of ethanol, and increased Bdnf expression in the ventral tegmental area (VTA) compared to control-sired male offspring. There were no differences among ethanol- and control-sired female offspring on these assays. Ethanol exposure also decreased DNA methylation at the BdnfÆpromoter of sire's germ cells and hypomethylation was maintained in the VTA of both male and female ethanol-sired offspring. Our findings show that paternal alcohol exposure is a previously unrecognized regulator of alcohol drinking and behavioral sensitivity to alcohol in male, but not female, offspring. Paternal alcohol exposure also induces epigenetic alterations (DNA hypomethylation) and gene expression changes that persist in the VTA of offspring. These results provide new insight into the inheritance and development of alcohol drinking behaviors. PMID:24896617

  16. Paternal alcohol exposure reduces alcohol drinking and increases behavioral sensitivity to alcohol selectively in male offspring.

    PubMed

    Finegersh, Andrey; Homanics, Gregg E

    2014-01-01

    Alcohol use disorder (AUD) is heritable, but the genetic basis for this disease remains poorly understood. Although numerous gene variants have been associated with AUD, these variants account for only a small fraction of the total risk. The idea of inheritance of acquired characteristics, i.e. "epigenetic inheritance," is re-emerging as a proven adjunct to traditional modes of genetic inheritance. We hypothesized that alcohol drinking and neurobiological sensitivity to alcohol are influenced by ancestral alcohol exposure. To test this hypothesis, we exposed male mice to chronic vapor ethanol or control conditions, mated them to ethanol-naïve females, and tested adult offspring for ethanol drinking, ethanol-induced behaviors, gene expression, and DNA methylation. We found that ethanol-sired male offspring had reduced ethanol preference and consumption, enhanced sensitivity to the anxiolytic and motor-enhancing effects of ethanol, and increased Bdnf expression in the ventral tegmental area (VTA) compared to control-sired male offspring. There were no differences among ethanol- and control-sired female offspring on these assays. Ethanol exposure also decreased DNA methylation at the BdnfÆpromoter of sire's germ cells and hypomethylation was maintained in the VTA of both male and female ethanol-sired offspring. Our findings show that paternal alcohol exposure is a previously unrecognized regulator of alcohol drinking and behavioral sensitivity to alcohol in male, but not female, offspring. Paternal alcohol exposure also induces epigenetic alterations (DNA hypomethylation) and gene expression changes that persist in the VTA of offspring. These results provide new insight into the inheritance and development of alcohol drinking behaviors.

  17. Different alcohol exposures induce selective alterations on the expression of dynorphin and nociceptin systems related genes in rat brain.

    PubMed

    D'Addario, Claudio; Caputi, Francesca F; Rimondini, Roberto; Gandolfi, Ottavio; Del Borrello, Elia; Candeletti, Sanzio; Romualdi, Patrizia

    2013-05-01

    Molecular mechanisms of adaptive transformations caused by alcohol exposure on opioid dynorphin and nociceptin systems have been investigated in the rat brain. Alcohol was intragastrically administered to rats to resemble human drinking with several hours of exposure: water or alcohol (20% in water) at a dose of 1.5 g/kg three times daily for 1 or 5 days. The development of tolerance and dependence were recorded daily. Brains were dissected 30 minutes (1- and 5-day groups) or 1, 3 or 7 days after the last administration for the three other 5-day groups (groups under withdrawal). Specific alterations in opioid genes expression were ascertained. In the amygdala, an up-regulation of prodynorphin and pronociceptin was observed in the 1-day group; moreover, pronociceptin and the kappa opioid receptor mRNAs in the 5-day group and both peptide precursors in the 1-day withdrawal group were also up-regulated. In the prefrontal cortex, an increase in prodynorhin expression in the 1-day group was detected. These data indicate a relevant role of the dynorphinergic system in the negative hedonic states associated with multiple alcohol exposure. The pattern of alterations observed for the nociceptin system appears to be consistent with its role of functional antagonism towards the actions of ethanol associated with other opioid peptides. Our findings could help to the understanding of how alcohol differentially affects the opioid systems in the brain and also suggest the dynorphin and nociceptin systems as possible targets for the treatment and/or prevention of alcohol dependence.

  18. The use of a selective serotonin reuptake inhibitor decreases heavy alcohol exposure-induced inflammatory response and tissue damage in rats.

    PubMed

    Hu, Tsung M; Subeq, Yi M; Yang, Fwu L; Hsu, Bang G; Lin, Nien T; Lee, Ru P

    2013-10-01

    Alcohol intoxication and psychiatric medication overdoses, including antidepressants, are common emergency room events. Heavy alcohol and antidepressant exposure are able to induce changes in cytokines disturbing normal physiology. We examined the inflammatory and physiological effects of selective serotonin reuptake inhibitor (SSRI) medication after heavy alcohol exposure. Rats were randomly divided into Alc (EtOH 5g/kg, intravenous infusion for 3 h), SSRI (paroxetine oral intake) and Alc+SSRI groups. Serum samples were collected to measure blood ethanol, aspartate transferase, alanine transferase, creatine phosphokinase, lactate dehydrogenase, amylase, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels. Lactate dehydrogenase levels in bronchoalveolar lavage fluid were also examined. Liver, pancreas and lungs were removed after sacrifice and any pathological changes were catalogued. Ethanol infusion resulted in blood levels of ethanol of >100 mg/dL after ethanol infusion. Serum levels of aspartate transferase, alanine transferase, creatine phosphokinase, lactate dehydrogenase, amylase, TNF-α and IL-6 in the Alc+SSRI group were lower than in the Alc group. Moreover, pathological damages to the liver, pancreas and lungs were slightly lower in the Alc+SSRI group than in the Alc group. These findings suggested that SSRI is able to decrease the release of pro-inflammatory cytokines and thereby reduce liver and pancreas damage after heavy alcohol exposure.

  19. Psychiatric Conditions Associated with Prenatal Alcohol Exposure

    ERIC Educational Resources Information Center

    O'Connor, Mary J.; Paley, Blair

    2009-01-01

    Since the identification of fetal alcohol syndrome (FAS) over 35 years ago, mounting evidence about the impact of maternal alcohol consumption during pregnancy has prompted increased attention to the link between prenatal alcohol exposure (PAE) and a constellation of developmental disabilities that are characterized by physical, cognitive, and…

  20. Chronic alcohol exposure induces muscle atrophy (myopathy) in zebrafish and alters the expression of microRNAs targeting the Notch pathway in skeletal muscle.

    PubMed

    Khayrullin, Andrew; Smith, Lauren; Mistry, Dhwani; Dukes, Amy; Pan, Y Albert; Hamrick, Mark W

    2016-10-21

    Muscle wasting is estimated to affect 40-60% of alcoholics, and is more common than cirrhosis among chronic alcohol abusers. The molecular and cellular mechanisms underlying alcohol-related musculoskeletal dysfunction are, however, poorly understood. Muscle-specific microRNAs (miRNAs) referred to as myoMirs are now known to play a key role in both myogenesis and muscle atrophy. Yet, no studies have investigated a role for myoMirs in alcohol-related skeletal muscle damage. We developed a zebrafish model of chronic ethanol exposure to better define the mechanisms mediating alcohol-induced muscle atrophy. Adult fish maintained at 0.5% ethanol for eight weeks demonstrated significantly reduced muscle fiber cross-sectional area (∼12%, P < 0.05) compared to fish housed in normal water. Zebrafish miRNA microarray revealed marked changes in several miRNAs with ethanol treatment. Importantly, miR-140, a miRNA that shows 100% sequence homology with miR-140 from both mouse and human, is decreased 10-fold in ethanol treated fish. miR-140 targets several members of the Notch signaling pathway such as DNER, JAG1, and Hey1, and PCR data show that both Hey1 and Notch 1 are significantly up-related (3-fold) in muscle of ethanol treated fish. In addition, miR-146a, which targets the Notch antagonist Numb, is elevated in muscle from ethanol-treated fish. Upregulation of Notch signaling suppresses myogenesis and maintains muscle satellite cell quiescence. These data suggest that miRNAs targeting Notch are likely to play important roles in alcohol-related myopathy. Furthermore, zebrafish may serve as a useful model for better understanding the role of microRNAs in alcohol-related tissue damage.

  1. Intermittent binge alcohol exposure during the periadolescent period induces spatial working memory deficits in young adult rats.

    PubMed

    Schulteis, Gery; Archer, Clay; Tapert, Susan F; Frank, Lawrence R

    2008-09-01

    Human and animal studies suggest adolescence is a period of heightened sensitivity to adverse cognitive sequelae of alcohol exposure. The present study assessed the effects of intermittent binge ethanol intoxication during the periadolescent period of Wistar rats on subsequent performance in a Morris water maze spatial navigation task. On postnatal days 32-56, rats were exposed to ethanol or air 3 days/week via vapor inhalation chambers. Acquisition of spatial navigation was assessed beginning 5 days after the final day of exposure, with 3 days of training in the Morris Water maze (four trials per day spaced at 90-s intertrial intervals [ITIs]). Rats were placed into the water maze at one of four positions along the perimeter, with a different release position to begin each trial. A probe trial assessed retention of platform location on the day after the final set of training trials. Four days after this probe trial, rats entered a working memory phase in which the platform was in a new location each day and a variable ITI of 1, 2, or 4 h was inserted between Trials 1 and 2; Trials 3 and 4 followed at 90-s intervals after Trial 2 on each day. The "savings" in latency to find the platform and distance traveled before finding it from Trial 1 to Trial 2 on each day served as an index of working memory. Ethanol-exposed rats showed similar acquisition of spatial navigation as control rats during training, as well as similar retention of platform location during the probe trial. However, rats exposed to average blood alcohol level (BAL) >200 mg% showed accelerated forgetting, with decreased retention of platform location at the 2-h ITI (P < .05), compared to control rats. Therefore, a 4-week history of intermittent ethanol exposure at BAL in excess of 200 mg% during periadolescence led to a working memory deficit in young adult rats, demonstrated by accelerated forgetting of novel information. These behavioral data are consistent with findings from adolescent human

  2. Operant Responding for Alcohol Following Alcohol Cue Exposure in Social Drinkers

    PubMed Central

    Van Dyke, Nicholas; Fillmore, Mark T.

    2015-01-01

    Introduction Cue reactivity paradigms have found that alcohol-related cues increase alcohol consumption in heavy drinkers and alcoholics. However, evidence of this relationship among non-alcohol dependent “social” drinkers is mixed, suggesting that individual differences must be considered when examining cue-induced drinking behavior. One important individual difference factor that might contribute to cue-induced drinking in the laboratory is the amount of alcohol that participants typically drink during occasions outside the laboratory. That is, those who typically consume more alcohol per occasion could display greater cue-induced drinking than those who typically drink less. The present study examined this hypothesis in healthy, non-dependent beer drinkers. Methods The drinkers were exposed to either a series of beer images intended to prime their motivation to drink beer or to a series of non-alcoholic images of food items that served as a control condition. Following cue exposure, motivation to drink was measured by giving participants an opportunity to work for glasses of beer by performing an operant response task. Results Results indicated that drinkers exposed to alcohol cues displayed greater operant responding for alcohol and earned more drinks compared with those exposed to non-alcohol (i.e., food) cues. Moreover, individual differences in drinking habits predicted subjects’ responding for alcohol following exposure to the alcohol cues, but not following exposure to food cues. Conclusions The findings suggest that cue-induced drinking in non-dependent drinkers likely results in consumption levels commensurate with their typical consumption outside the laboratory, but not excessive consumption that is sometimes observed in alcohol-dependent samples. PMID:25841089

  3. Early exposure to ethanol but not red wine at the same alcohol concentration induces behavioral and brain neurotrophin alterations in young and adult mice.

    PubMed

    Fiore, Marco; Laviola, Giovanni; Aloe, Luigi; di Fausto, Veronica; Mancinelli, Rosanna; Ceccanti, Mauro

    2009-01-01

    Ethanol exposure during pregnancy is one of the major causes of mental retardation in western countries by inducing fetal-alcohol-like-syndromes. Red wine is known to contain ethanol but also compounds with putative antioxidant properties. It has also been shown that nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are severely affected by ethanol during prenatal and postnatal life. The aim of the current study was to investigate in male CD1 mice brain alterations in NGF and BDNF due to chronic early exposure to ethanol solution (11 vol%) or to red wine at the same alcohol concentration starting from 60 days before pregnancy up to pups weaning. Data revealed no differences between groups of dams in pregnancy duration, neither in pups delivery, pups mortality and sex ratio. Data also showed that adult animals exposed to only ethanol had disrupted levels of both NGF and BDNF in the hippocampus and other brain areas. This profile was associated with impaired ChAT immunopositivity in the septum and Nuclei Basalis and with altered cognition and emotional behavior. Quite interestingly mice exposed to red wine had no change in the behavior or in ChAT immunopositivity but a decrease in hippocampal BDNF and a mild NGF decrease in the cortex. Also NGF-induced neuritic outgrowth in PC-12 cells was still present when exposed to red wine but not when exposed to ethanol solution only. Data suggest differences in ethanol-induced neurotoxicity between red wine and ethanol solution only.

  4. Alcohol exposure during development: Impact on the epigenome.

    PubMed

    Perkins, Amy; Lehmann, Claudia; Lawrence, R Charles; Kelly, Sandra J

    2013-10-01

    Fetal alcohol spectrum disorders represent a wide range of symptoms associated with in utero alcohol exposure. Animal models of FASD have been useful in determining the specific neurological consequences of developmental alcohol exposure, but the mechanisms of those consequences are unclear. Long-lasting changes to the epigenome are proposed as a mechanism of alcohol-induced teratogenesis in the hippocampus. The current study utilized a three-trimester rodent model of FASD to examine changes to some of the enzymatic regulators of the epigenome in adolescence. Combined pre- and post-natal alcohol exposureresulted in a significant increase in DNA methyltransferase activity (DNMT), without affecting histone deacetylase activity (HDAC). Developmental alcohol exposure also caused a change in gene expression of regulators of the epigenome, in particular, DNMT1, DNMT3a, and methyl CpG binding protein 2 (MeCP2). The modifications of the activity and expression of epigenetic regulators in the hippocampus of rodents perinatally exposed to alcohol suggest that alcohol's impact on the epigenome and its regulators may be one of the underlying mechanisms of alcohol teratogenesis.

  5. Photobiomodulation on alcohol induced dysfunction

    NASA Astrophysics Data System (ADS)

    Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

    2007-05-01

    Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

  6. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish

    PubMed Central

    Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an “inverted V” dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure. PMID:26558894

  7. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

    PubMed

    Li, Xiang; Li, Xu; Li, Yi-Xiang; Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

  8. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    SciTech Connect

    Wahlang, Banrida; Song, Ming; Beier, Juliane I.; Cameron Falkner, K.; Al-Eryani, Laila; Clair, Heather B.; Prough, Russell A.; Osborne, Tanasa S.; Malarkey, David E.; Christopher States, J.; Cave, Matthew C.

    2014-09-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced

  9. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    PubMed Central

    Wahlang, Banrida; Song, Ming; Beier, Juliane I.; Falkner, K. Cameron; Al-Eryani, Laila; Clair, Heather B.; Prough, Russell A.; Osborne, Tanasa S.; Malarkey, David E.; States, J. Christopher; Cave, Matthew C.

    2014-01-01

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. PMID:24998970

  10. Alcohol dehydrogenase and cytochrome P450 2E1 can be induced by long-term exposure to ethanol in cultured liver HEP-G2 cells.

    PubMed

    Balusikova, Kamila; Kovar, Jan

    2013-09-01

    It has been shown in previous studies that liver HEP-G2 cells (human hepatocellular carcinoma) lose their ability to express active alcohol dehydrogenase (ADH) and cytochrome P450 2E1 (CYP2E1). Although both are ethanol-inducible enzymes, short-term exposure to ethanol does not cause any changes in expression or activity in cultured HEP-G2 cells. Therefore, we tested the effect of long-term exposure to ethanol on the expression and activity of both ADH and CYP2E1 in these cells. The expression of ADH and CYP2E1 was assessed at the mRNA and/or protein level using real-time PCR and Western blot analysis. Specific colorimetric assays were used for the measurement of ADH and CYP2E1 enzymatic activities. Caco-2 cells (active CYP2E1 and inactive ADH) were used as control cells. Significantly increased protein expression of ADH (about 2.5-fold) as well as CYP2E1 (about 1.6-fold) was found in HEP-G2 cells after long-term (12 mo) exposure to ethanol. The activity of ADH and CYP2E1 was also significantly increased from 12 ± 3 and 6 ± 1 nmol/h/mg of total protein to 191 ± 9 and 57 ± 9 nmol/h/mg of total protein, respectively. We suggest that the loss of activity of ethanol-metabolizing enzymes in cultured HEP-G2 cells is reversible and can be induced by prolonged exposure to ethanol. We are therefore able to reactivate HEP-G2 cells metabolic functions concerning ethanol oxidation just by modification of in vitro culture conditions without necessity of transfection with its side effect - enzyme overexpression.

  11. Alcohol exposure in utero perturbs retinoid homeostasis in adult rats

    PubMed Central

    Kim, Youn-Kyung; Zuccaro, Michael V.; Zhang, Changqing; Sarkar, Dipak

    2015-01-01

    Background Maternal alcohol exposure and adult alcohol intake have been shown to perturb the metabolism of various micro- and macro-nutrients, including vitamin A and its derivatives (retinoids). Therefore, it has been hypothesized that the well-known detrimental consequences of alcohol consumption may be due to deregulations of the metabolism of such nutrients rather than to a direct effect of alcohol. Alcohol exposure in utero also has long-term harmful consequences on the health of the offspring with mechanisms that have not been fully clarified. Disruption of tissue retinoid homeostasis has been linked not only to abnormal embryonic development, but also to various adult pathological conditions, including cancer, metabolic disorders and abnormal lung function. We hypothesized that prenatal alcohol exposure may permanently perturb tissue retinoid metabolism, predisposing the offspring to adult chronic diseases. Methods Serum and tissues (liver, lung and prostate from males; liver and lung from females) were collected from 60-75 day-old sprague dawley rats born from dams that were: (I) fed a liquid diet containing 6.7% alcohol between gestational day 7 and 21; or (II) pair-fed with isocaloric liquid diet during the same gestational window; or (III) fed ad libitum with regular rat chow diet throughout pregnancy. Serum and tissue retinoid levels were analyzed by reverse-phase high-performance liquid chromatography (HPLC). Serum retinol-binding protein (RBP) levels were measured by western blot analysis, and liver, lung and prostate mRNA levels of lecithin-retinol acyltransferase (LRAT) were measured by qPCR. Results Retinyl ester levels were significantly reduced in the lung of both males and females, as well as in the liver and ventral prostate of males born from alcohol-fed dams. Tissue LRAT mRNA levels remained unchanged upon maternal alcohol treatment. Conclusions Prenatal alcohol exposure in rats affects retinoid metabolism in adult life, in a tissue- and sex

  12. Are You Insulting Me? Exposure to Alcohol Primes Increases Aggression Following Ambiguous Provocation

    PubMed Central

    Pedersen, William C.; Vasquez, Eduardo A.; Bartholow, Bruce D.; Grosvenor, Marianne; Truong, Ana

    2014-01-01

    Considerable research has shown that alcohol consumption can increase aggression and produce extremes in other social behaviors. Although most theories posit that such effects are caused by pharmacological impairment of cognitive processes, recent research indicates that exposure to alcohol-related constructs, in the absence of consumption, can produce similar effects. Here we tested the hypothesis that alcohol priming is most likely to affect aggression in the context of ambiguous provocation. Experiment 1 showed that exposure to alcohol primes increased aggressive retaliation but only when an initial provocation was ambiguous; unambiguous provocation elicited highly aggressive responses regardless of prime exposure. Experiment 2 showed that alcohol prime exposure effects are relatively short-lived and that perceptions of the provocateur's hostility mediated effects of prime exposure on aggression. These findings suggest modification and extension of existing models of alcohol-induced aggression. PMID:24854477

  13. Enhancement of placental antioxidative function and P-gp expression by sodium ferulate mediated its protective effect on rat IUGR induced by prenatal tobacco/alcohol exposure.

    PubMed

    Li, Yan; Yan, You-E; Wang, Hui

    2011-11-01

    This study was aimed to explore the therapeutic effect of sodium ferulate (SF) on rats with intrauterine growth retardation (IUGR), and then to clarify the corresponding mechanism. Pregnant rats were divided into normal group, tobacco/alcohol exposure group, and tobacco/alcohol+SF groups. Fetal developmental indices, placental weight, histological alteration, oxidative and antioxidative-function (e.g. MDA, SOD, CAT) and Mdr1 levels were assayed. Results showed exposure to tobacco/alcohol resulted in reduced fetal developmental indices and placental histological alteration, as well as the increased MDA content, decreased SOD and CAT activities and decreased Mdr1a level. After SF treatment, fetal developmental indices, and placental weight, histological alteration, oxidative and antioxidative-function and mdr1a levels were reversed. Our study indicated SF may be effective in reversing IUGR production, and its underlying mechanism may be due to enhanced placental antioxidative function and P-gp expression, which may be related to IUGR formation by tobacco/alcohol exposure.

  14. Race, Ethnicity, and Exposure to Alcohol Outlets

    PubMed Central

    Morrison, Christopher; Gruenewald, Paul J.; Ponicki, William R.

    2016-01-01

    Objective: Prior studies suggest that Black and Hispanic minority populations are exposed to greater concentrations of alcohol outlets, potentially contributing to health disparities between these populations and the White majority. We tested the alternative hypothesis that urban economic systems cause outlets to concentrate in low-income areas and, controlling for these effects, lower demand among minority populations leads to fewer outlets. Method: Market potential for alcohol sales, a surrogate for demand, was estimated from survey and census data across census block groups for 50 California cities. Hierarchical Bayesian conditional autoregressive Poisson models then estimated relationships between observed geographic distributions of outlets and the market potential for alcohol, income, population size, and racial and ethnic composition. Results: Market potentials were significantly smaller among lower income Black, Hispanic, and Asian populations. Block groups with greater market potential and lower income had greater concentrations of outlets. When we controlled for these effects, the racial and ethnic group composition of block groups was mostly unrelated to outlet concentrations. Conclusions: Health disparities related to exposure to alcohol outlets are primarily driven by distributions of income and population density across neighborhoods. PMID:26751356

  15. Exposure to Televised Alcohol Ads and Subsequent Adolescent Alcohol Use

    ERIC Educational Resources Information Center

    Stacy, Alan W.; Zogg, Jennifer B.; Unger, Jennifer B.; Dent, Clyde W.

    2004-01-01

    Objective : To assess the impact of televised alcohol commercials on adolescents' alcohol use. Methods : Adolescents completed questionnaires about alcohol commercials and alcohol use in a prospective study. Results : A one standard deviation increase in viewing television programs containing alcohol commercials in seventh grade was associated…

  16. Alcohol-cue exposure effects on craving and attentional bias in underage college-student drinkers.

    PubMed

    Ramirez, Jason J; Monti, Peter M; Colwill, Ruth M

    2015-06-01

    The effect of alcohol-cue exposure on eliciting craving has been well documented, and numerous theoretical models assert that craving is a clinically significant construct central to the motivation and maintenance of alcohol-seeking behavior. Furthermore, some theories propose a relationship between craving and attention, such that cue-induced increases in craving bias attention toward alcohol cues, which, in turn, perpetuates craving. This study examined the extent to which alcohol cues induce craving and bias attention toward alcohol cues among underage college-student drinkers. We designed within-subject cue-reactivity and visual-probe tasks to assess in vivo alcohol-cue exposure effects on craving and attentional bias on 39 undergraduate college drinkers (ages 18-20). Participants expressed greater subjective craving to drink alcohol following in vivo cue exposure to a commonly consumed beer compared with water exposure. Furthermore, following alcohol-cue exposure, participants exhibited greater attentional biases toward alcohol cues as measured by a visual-probe task. In addition to the cue-exposure effects on craving and attentional bias, within-subject differences in craving across sessions marginally predicted within-subject differences in attentional bias. Implications for both theory and practice are discussed. (PsycINFO Database Record

  17. Effects of methylmercury and alcohol exposure in Drosophila melanogaster: Potential risks in neurodevelopmental disorders.

    PubMed

    Chauhan, Ved; Chauhan, Abha

    2016-06-01

    Extensive evidence suggests the role of oxidative stress in autism and other neurodevelopmental disorders. In this study, we investigated whether methylmercury (MeHg) and/or alcohol exposure has deleterious effects in Drosophila melanogaster (fruit flies). A diet containing different concentrations of MeHg in Drosophila induced free radical generation and increased lipid peroxidation (markers of oxidative stress) in a dose-dependent manner. This effect of MeHg on oxidative stress was enhanced by further exposure to alcohol. It was observed that alcohol alone could also induce free radical generation in flies. After alcohol exposure, MeHg did not affect the immobilization of flies, but it increased the recovery time in a concentration-dependent manner. MeHg significantly inhibited the activity of alcohol dehydrogenase (ADH) in a dose-dependent manner. Linear regression analysis showed a significant negative correlation between ADH activity and recovery time upon alcohol exposure in the flies fed a diet with MeHg. This relationship between ADH activity and recovery time after alcohol exposure was confirmed by adding 4-methyl pyrazole (an inhibitor of ADH) to the diet for the flies. These results suggest that consumption of alcohol by pregnant mothers who are exposed to MeHg may lead to increased oxidative stress and to increased length of time for alcohol clearance, which may have a direct impact on the development of the fetus, thereby increasing the risk of neurodevelopmental disorders.

  18. Prenatal alcohol exposure increases postnatal acceptability of nicotine odor and taste in adolescent rats.

    PubMed

    Mantella, Nicole M; Youngentob, Steven L

    2014-01-01

    Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our

  19. Adolescent alcohol exposure: Are there separable vulnerable periods within adolescence?

    PubMed

    Spear, Linda Patia

    2015-09-01

    There are two key alcohol use patterns among human adolescents that confer increased vulnerability for later alcohol abuse/dependence, along with neurocognitive alterations: (a) early initiation of use during adolescence, and (b) high rates of binge drinking that are particularly prevalent late in adolescence. The central thesis of this review is that lasting neurobehavioral outcomes of these two adolescent exposure patterns may differ. Although it is difficult to disentangle consequences of early use from later binge drinking in human studies given the substantial overlap between groups, these two types of problematic adolescent use are differentially heritable and hence separable to some extent. Although few studies using animal models have manipulated alcohol exposure age, those studies that have have typically observed timing-specific exposure effects, with more marked (or at least different patterns of) lasting consequences evident after exposures during early-mid adolescence than late-adolescence/emerging adulthood, and effects often restricted to male rats in those few instances where sex differences have been explored. As one example, adult male rats exposed to ethanol during early-mid adolescence (postnatal days [P] 25-45) were found to be socially anxious and to retain adolescent-typical ethanol-induced social facilitation into adulthood, effects that were not evident after exposure during late-adolescence/emerging adulthood (P45-65); exposure at the later interval, however, induced lasting tolerance to ethanol's social inhibitory effects that was not evident after exposure early in adolescence. Females, in contrast, were little influenced by ethanol exposure at either interval. Exposure timing effects have likewise been reported following social isolation as well as after repeated exposure to other drugs such as nicotine (and cannabinoids), with effects often, although not always, more pronounced in males where studied. Consistent with these timing

  20. Alcohol-Induced Histone Acetylation Reveals a Gene Network Involved in Alcohol Tolerance

    PubMed Central

    Ghezzi, Alfredo; Krishnan, Harish R.; Lew, Linda; Prado, Francisco J.; Ong, Darryl S.; Atkinson, Nigel S.

    2013-01-01

    Sustained or repeated exposure to sedating drugs, such as alcohol, triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Alcohol-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most of which may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct alcohols. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol. PMID:24348266

  1. Adolescent Alcohol Exposure: Burden of Epigenetic Reprogramming, Synaptic Remodeling, and Adult Psychopathology

    PubMed Central

    Kyzar, Evan J.; Floreani, Christina; Teppen, Tara L.; Pandey, Subhash C.

    2016-01-01

    Adolescence represents a crucial phase of synaptic maturation characterized by molecular changes in the developing brain that shape normal behavioral patterns. Epigenetic mechanisms play an important role in these neuromaturation processes. Perturbations of normal epigenetic programming during adolescence by ethanol can disrupt these molecular events, leading to synaptic remodeling and abnormal adult behaviors. Repeated exposure to binge levels of alcohol increases the risk for alcohol use disorder (AUD) and comorbid psychopathology including anxiety in adulthood. Recent studies in the field clearly suggest that adolescent alcohol exposure causes widespread and persistent changes in epigenetic, neurotrophic, and neuroimmune pathways in the brain. These changes are manifested by altered synaptic remodeling and neurogenesis in key brain regions leading to adult psychopathology such as anxiety and alcoholism. This review details the molecular mechanisms underlying adolescent alcohol exposure-induced changes in synaptic plasticity and the development of alcohol addiction-related phenotypes in adulthood. PMID:27303256

  2. Prenatal alcohol exposure, blood alcohol concentrations and alcohol elimination rates for the mother, fetus and newborn.

    PubMed

    Burd, L; Blair, J; Dropps, K

    2012-09-01

    Fetal alcohol spectrum disorders (FASDs) are a common cause of intellectual impairment and birth defects. More recently, prenatal alcohol exposure (PAE) has been found to be a risk factor for fetal mortality, stillbirth and infant and child mortality. This has led to increased concern about detection and management of PAE. One to 2 h after maternal ingestion, fetal blood alcohol concentrations (BACs) reach levels nearly equivalent to maternal levels. Ethanol elimination by the fetus is impaired because of reduced metabolic capacity. Fetal exposure time is prolonged owing to the reuptake of amniotic-fluid containing ethanol by the fetus. Alcohol elimination from the fetus relies on the mother's metabolic capacity. Metabolic capacity among pregnant women varies eightfold (from 0.0025 to 0.02 g dl(-1)  h(-1)), which may help explain how similar amounts of ethanol consumption during pregnancy results in widely varying phenotypic presentations of FASD. At birth physiological changes alter the neonate's metabolic capacity and it rapidly rises to a mean value of 83.5% of the mother's capacity. FASDs are highly recurrent and younger siblings have increased risk. Detection of prenatal alcohol use offers an important opportunity for office-based interventions to decrease exposure for the remainder of pregnancy and identification of women who need substance abuse treatment. Mothers of children with FAS have been found to drink faster, get drunk quicker and to have higher BACs. A modest increase in the prevalence of a polymorphism of alcohol dehydrogenase, which increases susceptibility to adverse outcomes from PAE has been reported. Lastly, detection of alcohol use and appropriate management would decrease risk from PAE for subsequent pregnancies.

  3. Media exposure and marijuana and alcohol use among adolescents.

    PubMed

    Primack, Brian A; Kraemer, Kevin L; Fine, Michael J; Dalton, Madeline A

    2009-01-01

    We aimed to determine which media exposures are most strongly associated with marijuana and alcohol use among adolescents. In 2004, we surveyed 1,211 students at a large high school in suburban Pittsburgh regarding substance use, exposure to entertainment media, and covariates. Of the respondents, 52% were female, 8% were non-White, 27% reported smoking marijuana, and 60% reported using alcohol. They reported average exposure to 8.6 hr of media daily. In adjusted models, exposure to music was independently associated with marijuana use, but exposure to movies was independently associated with alcohol use. Implications, limitations, and suggestions for further research are discussed.

  4. Prenatal Alcohol Exposure Damages Brain Signal Transduction System

    DTIC Science & Technology

    2004-09-01

    phosphatidylinositol-specific Materials and methods phospholipase C isozymes, phospholipase C-71, found in rodent brain. Phospholipase C isozymes catalyze...alcohol syndrome and animal models of fetal alcohol exposure (FAE). alcohol-related neurodevelopmental disorder (Streissguth Most studies on fetal alcohol...1999). In learning and memory deficits. In rodents , FAE is associated our study, the 10% ethanol mice reacted to the presenta- with impaired learning

  5. Factors associated with younger adolescents' exposure to online alcohol advertising.

    PubMed

    D'Amico, Elizabeth J; Martino, Steven C; Collins, Rebecca L; Shadel, William G; Tolpadi, Anagha; Kovalchik, Stephanie; Becker, Kirsten M

    2017-03-01

    Little is known about the extent and nature of youth exposure to online alcohol advertising, or factors that may be associated with exposure. The current study recruited middle school students who completed a paper survey and then logged each alcohol advertisement that they encountered over a 2-week period using cell phones as part of an ecological momentary assessment design. We examined the percentage of youth who reported exposure to online alcohol advertising in the past 2 weeks, average weekly rate of exposure, types of online alcohol advertisements youth reported seeing, and factors that increased youths' risk of exposure to online alcohol advertising. Analyses are based on 485 participants (47% female; 25% Hispanic, 25% White, 27% Black; 6% Asian, 16% other). Youth logged exposures to a total of 3,966 (16,018 weighted for underreporting) alcohol advertisements across the monitoring period; 154 (568 weighted) or 3.6% were online ads. Seventeen percent of youth reported seeing any online alcohol ad; the majority of online ads seen were video commercials (44.8%) and banner/side ads (26.6%). Factors associated with greater ad exposure were being older, rebellious, and Black race; greater parental monitoring and more hours spent on social media were associated with less exposure. Findings provide important information about adolescents' exposure to online alcohol advertising and what might contribute to a greater likelihood of exposure. Given that online ad exposure is linked to drinking behavior, prevention programming for younger adolescents should continue to address this issue to help youth make healthy choices regarding alcohol use. (PsycINFO Database Record

  6. Impairment of social behaviour persists two years after embryonic alcohol exposure in zebrafish: A model of fetal alcohol spectrum disorders.

    PubMed

    Fernandes, Yohaan; Rampersad, Mindy; Gerlai, Robert

    2015-10-01

    Zebrafish naturally form social groups called shoals. Previously, we have shown that submerging zebrafish eggs into low concentrations of alcohol (0.00, 0.25, 0.50, 0.75 and 1.00 vol/vol% external bath concentration) during development (24h post-fertilization) for two hours resulted in impaired shoaling response in seven month old young adult zebrafish. Here we investigate whether this embryonic alcohol exposure induced behavioural deficit persists to older age. Zebrafish embryos were exposed either to fresh system water (control) or to 1% alcohol for two hours, 24h after fertilization, and were raised in a high-density tank system. Social behaviour was tested by presenting the experimental fish with a computer animated group of zebrafish images, while automated tracking software measured their behaviour. Control fish were found to respond strongly to animated conspecific images by reducing their distanceand remaining close to the images during image presentation, embryonic alcohol treated fish did not. Our results suggest that the impaired shoaling response of the alcohol exposed fish was not due to altered motor function or visual perception, but likely to a central nervous system alteration affecting social behaviour itself. We found the effects of embryonic alcohol exposure on social behaviour not to diminish with age, a result that demonstrates the deleterious and potentially life-long consequences of exposure to even small amount of alcohol during embryonic development in vertebrates.

  7. Communication Effects of Prenatal Alcohol Exposure.

    ERIC Educational Resources Information Center

    Abkarian, G. G.

    1992-01-01

    This literature review addresses studies of speech, language, and communication skills evidenced by children diagnosed with fetal alcohol syndrome and fetal alcohol effects. Concomitant physical, behavioral, intellectual, and learning patterns are reviewed, and symptoms presented by alcohol-exposed children are compared to those seen in other…

  8. Prenatal Alcohol Exposure and the Developing Immune System.

    PubMed

    Gauthier, Theresa W

    2015-01-01

    Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensive knowledge of the mechanisms underlying alcohol's effects on the developing immune system only will become clear once researchers establish improved methods for identifying newborns exposed to alcohol in utero.

  9. Prenatal Alcohol Exposure Selectively Enhances Young Adult Perceived Pleasantness of Alcohol Odors

    PubMed Central

    Hannigan, John H.; Chiodo, Lisa M.; Sokol, Robert J.; Janisse, James; Delaney-Black, Virginia

    2015-01-01

    Prenatal Alcohol Exposure (PAE) can lead to life-long neurobehavioral and social problems that can include a greater likelihood of early use and/or abuse of alcohol compared to older teens and young adults without PAE. Basic research in animals demonstrates that PAE influences later postnatal responses to chemosensory cues (i.e., odor & taste) associated with alcohol. We hypothesized that PAE would be related to poorer abilities to identify odors of alcohol-containing beverages, and would alter perceived alcohol odor intensity and pleasantness. To address this hypothesis we examined responses to alcohol and other odors in a small sample of young adults with detailed prenatal histories of exposure to alcohol and other drugs. The key finding from our controlled analyses is that higher levels of PAE were related to higher relative ratings of pleasantness for alcohol odors. As far as we are aware, this is the first published study to report the influence of PAE on responses to alcohol beverage odors in young adults. These findings are consistent with the hypothesis that positive associations (i.e., “pleasantness”) to the chemosensory properties of alcohol (i.e., odor) are acquired prenatally and are retained for many years despite myriad interceding postnatal experiences. Alternate hypotheses may also be supported by the results. There are potential implications of altered alcohol odor responses for understanding individual differences in initiation of drinking, and alcohol seeking and high-risk alcohol-related behaviors in young adults. PMID:25600468

  10. Movie exposure to alcohol cues and adolescent alcohol problems: a longitudinal analysis in a national sample.

    PubMed

    Wills, Thomas A; Sargent, James D; Gibbons, Frederick X; Gerrard, Meg; Stoolmiller, Mike

    2009-03-01

    The authors tested a theoretical model of how exposure to alcohol cues in movies predicts level of alcohol use (ever use plus ever and recent binge drinking) and alcohol-related problems. A national sample of younger adolescents was interviewed by telephone with 4 repeated assessments spaced at 8-month intervals. A structural equation modeling analysis performed for ever-drinkers at Time 3 (N = 961) indicated that, controlling for a number of covariates, movie alcohol exposure at Time 1 was related to increases in peer alcohol use and adolescent alcohol use at Time 2. Movie exposure had indirect effects to alcohol use and problems at Times 3 and 4 through these pathways, with direct effects to problems from Time 1 rebelliousness and Time 2 movie exposure also found. Prospective risk-promoting effects were also found for alcohol expectancies, peer alcohol use, and availability of alcohol in the home; protective effects were found for mother's responsiveness and for adolescent's school performance and self-control. Theoretical and practical implications are discussed. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

  11. Movie Exposure to Alcohol Cues and Adolescent Alcohol Problems: A Longitudinal Analysis in a National Sample

    PubMed Central

    Wills, Thomas A.; Sargent, James D.; Gibbons, Frederick X.; Gerrard, Meg; Stoolmiller, Mike

    2009-01-01

    The authors tested a theoretical model of how exposure to alcohol cues in movies predicts level of alcohol use (ever use plus ever and recent binge drinking) and alcohol-related problems. A national sample of younger adolescents was interviewed by telephone with 4 repeated assessments spaced at 8-month intervals. A structural equation modeling analysis performed for ever-drinkers at Time 3 (N = 961) indicated that, controlling for a number of covariates, movie alcohol exposure at Time 1 was related to increases in peer alcohol use and adolescent alcohol use at Time 2. Movie exposure had indirect effects to alcohol use and problems at Times 3 and 4 through these pathways, with direct effects to problems from Time 1 rebelliousness and Time 2 movie exposure also found. Prospective risk-promoting effects were also found for alcohol expectancies, peer alcohol use, and availability of alcohol in the home; protective effects were found for mother’s responsiveness and for adolescent’s school performance and self-control. Theoretical and practical implications are discussed. PMID:19290687

  12. Alcohol Exposure after Mild Focal Traumatic Brain Injury Impairs Neurological Recovery and Exacerbates Localized Neuroinflammation

    PubMed Central

    Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E

    2014-01-01

    Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (~300 g) were subjected to a mild focal TBI by lateral fluid percussion (~30 PSI, ~25 ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on /10h off; BAL~200 mg/dL) or room air for 10 days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation. PMID:25489880

  13. Alcohol exposure after mild focal traumatic brain injury impairs neurological recovery and exacerbates localized neuroinflammation.

    PubMed

    Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E

    2015-03-01

    Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (∼300g) were subjected to a mild focal TBI by lateral fluid percussion (∼30PSI, ∼25ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on/10h off; BAL∼200mg/dL) or room air for 10days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation.

  14. Ataxia induced by small amounts of alcohol

    PubMed Central

    Setta, F; Jacquy, J; Hildebrand, J; Manto, M

    1998-01-01

    A patient is described who exhibited cerebellar ataxia after drinking small amounts of alcohol. Intake of 5 g alcohol induced a gaze evoked nystagmus, a scanning speech, a body sway after eye closure, and bilateral postural leg tremor. Kinematic and EMG analysis of fast wrist movements showed normal movements before and marked hypermetria after alcohol intake. Dysmetria was due to abnormal programming of antagonist muscle activity.

 PMID:9728953

  15. A role for histone acetylation mechanisms in adolescent alcohol exposure-induced deficits in hippocampal brain-derived neurotrophic factor expression and neurogenesis markers in adulthood.

    PubMed

    Sakharkar, Amul J; Vetreno, Ryan P; Zhang, Huaibo; Kokare, Dadasaheb M; Crews, Fulton T; Pandey, Subhash C

    2016-12-01

    Binge drinking during adolescence is a risk factor for neuropsychiatric disorders that can develop later in life. Histone acetylation is an important epigenetic mechanism that contributes to neurodevelopment. We investigated the effects of adolescent intermittent ethanol (AIE) exposure, as opposed to normal saline (AIS) exposure, on histone acetylation-mediated regulation of brain-derived neurotrophic factor (BDNF) expression and developmental stages of neurogenesis (proliferating and immature neurons) in the hippocampus in adulthood. AIE exposure increased whole hippocampal histone deacetylase (HDAC) activity and decreased binding protein of cyclic adenosine monophosphate response element binding protein (CBP) and histone H3-K9 acetylation levels in the CA1, CA2, and CA3 regions of the hippocampus. BDNF protein and exon IV mRNA levels in the CA1 and CA3 regions of the hippocampus of AIE-exposed adult rats were decreased as compared to AIS-exposed adult rats. AIE-induced anxiety-like behaviors and deficits in histone H3 acetylation at BDNF exon IV promoter in the hippocampus during adulthood, which were reversed by treatment with the HDAC inhibitor, trichostatin A (TSA). Similarly, neurogenesis was inhibited by AIE in adulthood as demonstrated by the decrease in Ki-67 and doublecortin (DCX)-positive cells in the dentate gyrus, which was normalized by TSA treatment. These results indicate that AIE exposure increases HDACs and decreases CBP levels that may be associated with a decrease in histone H3 acetylation in the hippocampus. These epigenetic changes potentially decrease BDNF expression and inhibit neurogenesis in the hippocampus that may be involved in AIE-induced behavioral abnormalities, including anxiety, in adulthood.

  16. Reducing youth exposure to alcohol ads: targeting public transit.

    PubMed

    Simon, Michele

    2008-07-01

    Underage drinking is a major public health problem. Youth drink more heavily than adults and are more vulnerable to the adverse effects of alcohol. Previous research has demonstrated the connection between alcohol advertising and underage drinking. Restricting outdoor advertising in general and transit ads in particular, represents an important opportunity to reduce youth exposure. To address this problem, the Marin Institute, an alcohol industry watchdog group in Northern California, conducted a survey of alcohol ads on San Francisco bus shelters. The survey received sufficient media attention to lead the billboard company, CBS Outdoor, into taking down the ads. Marin Institute also surveyed the 25 largest transit agencies; results showed that 75 percent of responding agencies currently have policies that ban alcohol advertising. However, as the experience in San Francisco demonstrated, having a policy on paper does not necessarily mean it is being followed. Communities must be diligent in holding accountable government officials, the alcohol industry, and the media companies through which advertising occurs.

  17. Autophagy in alcohol-induced liver diseases.

    PubMed

    Dolganiuc, Angela; Thomes, Paul G; Ding, Wen-Xing; Lemasters, John J; Donohue, Terrence M

    2012-08-01

    Alcohol is the most abused substance worldwide and a significant source of liver injury; the mechanisms of alcohol-induced liver disease are not fully understood. Significant cellular toxicity and impairment of protein synthesis and degradation occur in alcohol-exposed liver cells, along with changes in energy balance and modified responses to pathogens. Autophagy is the process of cellular catabolism through the lysosomal-dependent machinery, which maintains a balance among protein synthesis, degradation, and recycling of self. Autophagy is part of normal homeostasis and it can be triggered by multiple factors that threaten cell integrity, including starvation, toxins, or pathogens. Multiple factors regulate autophagy; survival and preservation of cellular integrity at the expense of inadequately folded proteins and damaged high-energy generating intracellular organelles are prominent targets of autophagy in pathological conditions. Coincidentally, inadequately folded proteins accumulate and high-energy generating intracellular organelles, such as mitochondria, are damaged by alcohol abuse; these alcohol-induced pathological findings prompted investigation of the role of autophagy in the pathogenesis of alcohol-induced liver damage. Our review summarizes the current knowledge about the role and implications of autophagy in alcohol-induced liver disease.

  18. The margin of exposure to formaldehyde in alcoholic beverages.

    PubMed

    Monakhova, Yulia B; Jendral, Julien A; Lachenmeier, Dirk W

    2012-06-01

    Formaldehyde has been classified as carcinogenic to humans (WHO IARC group 1). It causes leukaemia and nasopharyngeal cancer, and was described to regularly occur in alcoholic beverages. However, its risk associated with consumption of alcohol has not been systematically studied, so this study will provide the first risk assessment of formaldehyde for consumers of alcoholic beverages.Human dietary intake of formaldehyde via alcoholic beverages in the European Union was estimated based on WHO alcohol consumption data and literature on formaldehyde contents of different beverage groups (beer, wine, spirits, and unrecorded alcohol). The risk assessment was conducted using the margin of exposure (MOE) approach with benchmark doses (BMD) for 10 % effect obtained from dose-response modelling of animal experiments.For tumours in male rats, a BMD of 30 mg kg(-1) body weight per day and a "BMD lower confidence limit" (BMDL) of 23 mg kg(-1) d(-1) were calculated from available long-term animal experiments. The average human exposure to formaldehyde from alcoholic beverages was estimated at 8·10(-5) mg kg(-1) d(-1). Comparing the human exposure with BMDL, the resulting MOE was above 200,000 for average scenarios. Even in the worst-case scenarios, the MOE was never below 10,000, which is considered to be the threshold for public health concerns.The risk assessment shows that the cancer risk from formaldehyde to the alcohol-consuming population is negligible and the priority for risk management (e.g. to reduce the contamination) is very low. The major risk in alcoholic beverages derives from ethanol and acetaldehyde.

  19. Agrp neuron activity is required for alcohol-induced overeating

    PubMed Central

    Cains, Sarah; Blomeley, Craig; Kollo, Mihaly; Rácz, Romeo; Burdakov, Denis

    2017-01-01

    Alcohol intake associates with overeating in humans. This overeating is a clinical concern, but its causes are puzzling, because alcohol (ethanol) is a calorie-dense nutrient, and calorie intake usually suppresses brain appetite signals. The biological factors necessary for ethanol-induced overeating remain unclear, and societal causes have been proposed. Here we show that core elements of the brain's feeding circuits—the hypothalamic Agrp neurons that are normally activated by starvation and evoke intense hunger—display electrical and biochemical hyperactivity on exposure to dietary doses of ethanol in brain slices. Furthermore, by circuit-specific chemogenetic interference in vivo, we find that the Agrp cell activity is essential for ethanol-induced overeating in the absence of societal factors, in single-housed mice. These data reveal how a widely consumed nutrient can paradoxically sustain brain starvation signals, and identify a biological factor required for appetite evoked by alcohol. PMID:28072397

  20. Effects of prolonged alcohol exposure on somatotrophs and corticotrophs in adult rats: Stereological and hormonal study.

    PubMed

    Trifunović, Svetlana; Manojlović-Stojanoski, Milica; Ristić, Nataša; Jurijević, Branka Šošić; Balind, Snežana Raus; Brajković, Gordana; Perčinić-Popovska, Florina; Milošević, Verica

    2016-05-01

    Exposure to alcohol alters many physiological processes, including endocrine status. The present study examined whether prolonged alcohol (A) exposure could modulate selected stereological and hormonal aspects of pituitary somatotrophs (growth hormone-GH cells) and corticotrophs (adrenocorticotropic hormone-ACTH cells) in adult rats. Changes in pituitary gland volume; the volume density, total number and volume of GH and ACTH cells following alcohol exposure were evaluated using a stereological system (newCAST), while peripheral GH and ACTH levels were determined biochemically. Our results demonstrated the reduction (p<0.05) of the volume density (37%) and volume of GH cells (29%) in the group A. Also, there was a tendency for the total number of GH cells to be smaller in the group A. Serum GH level was significantly decreased (p<0.05; 70%) in the group A when compared to control values. Moreover, prolonged alcohol exposure induced declines (p<0.05) in volume density (24%) and volume of ACTH cells (29%). The total number of ACTH cells and ACTH level were higher (p<0.05; 42%) in the group A than in control rats. Collectively, these results indicate that prolonged alcohol exposure leads not only to changes in GH and ACTH hormone levels, but also to alterations of the morphological aspects of GH and ACTH cells within the pituitary.

  1. Ecological Momentary Assessment of the Association Between Exposure to Alcohol Advertising and Early Adolescents' Beliefs About Alcohol

    PubMed Central

    Martino, Steven C.; Kovalchik, Stephanie A.; Collins, Rebecca L.; Becker, Kirsten M.; Shadel, William G.; D'Amico, Elizabeth J.

    2015-01-01

    Purpose To evaluate the momentary association between exposure to alcohol advertising and middle school students' beliefs about alcohol in real-world settings and to explore racial/ethnic differences in this association. Methods Middle school students (N = 588) carried handheld data collection devices for 14 days, recording their exposures to all forms of alcohol advertising during the assessment period. Students also responded to three investigator-initiated control prompts (programmed to occur randomly) on each day of the assessment period. After each exposure to advertising and at each control prompt, students reported their beliefs about alcohol. Mixed effects regression models compared students' beliefs about alcohol between moments of exposure to alcohol advertising and control prompts. Results Students perceived the typical person their age who drinks alcohol (prototype perceptions) more favorably and perceived alcohol use as more normative at times of exposure to alcohol advertising than at times of non-exposure (i.e., at control prompts). Exposure to alcohol advertising was not associated with shifts in the perceived norms of Black and Hispanic students, however, and the association between exposure and prototype perceptions was stronger among non-Hispanic students than among Hispanic students. Conclusions Exposure to alcohol advertising is associated with acute shifts in adolescents' perceptions of the typical person that drinks alcohol and the normativeness of drinking. These associations are both statistically and substantively meaningful. PMID:26480846

  2. Exposure to alcohol commercials in movie theaters affects actual alcohol consumption in young adult high weekly drinkers: an experimental study.

    PubMed

    Koordeman, Renske; Anschutz, Doeschka J; Engels, Rutger C M E

    2011-01-01

    The present pilot study examined the effects of alcohol commercials shown in movie theaters on the alcohol consumption of young adults who see these commercials. A two (alcohol commercials vs. nonalcohol commercials) by two (high weekly alcohol consumption vs. low weekly alcohol consumption) between-participant design was used, in which 184 young adults (age: 16-28 years) were exposed to a movie that was preceded by either alcohol commercials or nonalcohol commercials. Participants' actual alcohol consumption while watching the movie ("Watchmen") was examined. An analysis of variance (ANOVA) was conducted to examine the effects of the commercial condition on alcohol consumption. An interaction effect was found between commercial condition and weekly alcohol consumption (p < .001). Alcohol consumption among high weekly alcohol drinkers was higher in the alcohol commercial condition than in the nonalcohol commercial condition, whereas no differences were found in alcohol consumption between commercial conditions among low weekly alcohol drinkers. No gender differences were found in the association between exposure to alcohol commercials, weekly drinking, and alcohol use. Thus, exposure to alcohol commercials prior to a movie in a movie theater can directly influence alcohol consumption among high weekly alcohol consumers.

  3. Prenatal alcohol exposure and long-term developmental consequences

    SciTech Connect

    Spohr, H.L.; Willms, J. . Dept. of Pediatrics); Steinhausen, H.C. . Dept. of Child and Adolescent Psychiatry)

    1993-04-10

    Fetal alcohol syndrome (FAS) is a leading cause of congenital mental retardation but little is known about the long-term development and adolescent outcome of children with FAS. In a 10-year follow-up study of 60 patients diagnosed as having FAS in infancy and childhood, the authors investigated the long-term sequelae of intrauterine alcohol exposure. The authors found that the characteristic craniofacial malformations of FAS diminish with time, but microcephaly and, to a lesser degree, short stature and underweight (in boys) persist; in female adolescents body weight normalizes. Persistent mental retardation is the major sequela of intrauterine alcohol exposure in many cases, and environmental and educational factors do not have strong compensatory effects on the intellectual development of affected children.

  4. [Exposure to phtalates and their presence in alcoholic beverages].

    PubMed

    Jurica, Karlo; Uršulin-Trstenjak, Natalija; Vukić Lušić, Darija; Lušić, Dražen; Smit, Zdenko

    2013-06-01

    Phthalates are phthalic acid and aliphatic alcohol esters used as additives to plastic in order to improve its softness, flexibility, and elongation. Phthalates are highly mobile and migrate easily from plastic products into the environment due to their physical and chemical properties. This study briefly describes the characteristics and distribution of phthalates in the environment, their toxic effects on human health, the legislation regarding the maximum allowed concentration of phthalates in drinking water and products intended for infants, as well as the tolerable daily intake. Special attention is given to the methods of determining phthalates and their levels in alcoholic beverages, with an overview of phthalate occurrences and concentrations in plum brandy made in Croatia. A segment on denatured alcohol and illegally marketed alcohol is also included, as well as guidelines for the effective monitoring of the routes of human exposure to phthalates.

  5. Fetal Alcohol Exposure Reduces Adult Brain Plasticity. Science Briefs

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This Brief summarizes the findings and implications of "Moderate Fetal Alcohol Exposure Impairs the Neurogenic Response to an Enriched Environment in Adult Mice" (I. Y. Choi; A. M. Allan; and L. A. Cunningham). Observations of mice…

  6. Biomarkers for the Detection of Prenatal Alcohol Exposure: A Review.

    PubMed

    Bager, Heidi; Christensen, Lars Porskjaer; Husby, Steffen; Bjerregaard, Lene

    2017-02-01

    Alcohol exposure during pregnancy can cause adverse effects to the fetus, because it interferes with fetal development, leading to later physical and mental impairment. The most common clinical tool to determine fetal alcohol exposure is maternal self-reporting. However, a more objective and useful method is based on the use of biomarkers in biological specimens alone or in combination with maternal self-reporting. This review reports on clinically relevant biomarkers for detection of prenatal alcohol exposure (PAE). A systematic search was performed to ensure a proper overview in existing literature. Studies were selected to give an overview on clinically relevant neonatal and maternal biomarkers. The direct biomarkers fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), ethyl sulfate, and phosphatidylethanol (PEth) were found to be the most appropriate biomarkers in relation to detection of PAE. To review each biomarker in a clinical context, we have compared the advantages and disadvantages of each biomarker, in relation to its window of detectability, ease of collection, and the ease and cost of analysis of each biomarker. The biomarkers PEth, FAEEs, and EtG were found to be applicable for detection of even low levels of alcohol exposure. Meconium is an accessible matrix for determination of FAEEs and EtG, and blood an accessible matrix for determination of PEth.

  7. Functional significance of subjective response to alcohol across levels of alcohol exposure.

    PubMed

    Bujarski, Spencer; Hutchison, Kent E; Prause, Nicole; Ray, Lara A

    2017-01-01

    Pre-clinical neurobiological models of addiction etiology including both the allostatic model and incentive sensitization theory suggest that alcohol consumption among alcohol-dependent (AD) individuals will be dissociated from hedonic reward as positive reinforcement mechanisms wane in later stage dependence. The aims of this study are to test this claim in humans by examining the relationship between dimensions of subjective responses to alcohol (SR) and alcohol craving across levels of alcohol exposure. Non-treatment-seeking drinkers (n = 205) completed an i.v. alcohol challenge (final target breath alcohol concentration = 0.06 g/dl) and reported on SR and craving. Participants were classified as light-to-moderate drinkers (LMD), heavy drinkers (HD) or AD. Analyses examined group differences in SR and craving response magnitude, as well as concurrent and predictive associations between SR domains and craving. At baseline, LMD and AD reported greater stimulation than HD, which carried over post-alcohol administration. However, stimulation was dose-dependently associated with alcohol craving in HD only. Furthermore, lagged models found that stimulation preceded craving among HD only, whereas this hypothesized pattern of results was not observed for craving preceding stimulation. Sedation was also positively associated with craving, yet no group differences were observed. In agreement with the prediction of diminished positive reinforcement in alcohol dependence, this study showed that stimulation/hedonic reward from alcohol did not precede craving in AD, whereas stimulation was dose-dependently associated with and preceded craving among non-dependent HD.

  8. Alcohol exposure leads to unrecoverable cardiovascular defects along with edema and motor function changes in developing zebrafish larvae

    PubMed Central

    Li, Xu; Gao, Aiai; Wang, Yanan; Chen, Man; Peng, Jun; Yan, Huaying; Zhao, Xin; Feng, Xizeng

    2016-01-01

    ABSTRACT Maternal alcohol consumption during pregnancy can cause a series of developmental disorders in the fetus called FAS (fetal alcohol syndrome). In the present study we exposed zebrafish embryos to 1% and 2% alcohol and observed the morphology of heart and blood vessels during and after exposure to investigate motor function alterations, and damage and recovery to the cardiovascular system. The results showed that alcohol exposure could induce heart deformation, slower heart rate, and incomplete blood vessels and pericardium. After stopping exposure, larvae exposed to 1% alcohol could recover only in heart morphology, but larvae in 2% alcohol could not recover either morphology or function of cardiovascular system. The edema-like characteristics in the 2% alcohol group became more conspicuous afterwards, with destruction in the dorsal aorta, coarctation in segmental arteries and a decrease in motor function, implying more serious unrecoverable cardiovascular defects in the 2% group. The damaged blood vessels in the 2% alcohol group resulted in an alteration in permeability and a decrease of blood volume, which were the causes of edema in pathology. These findings contribute towards a better understanding of ethanol-induced cardiovascular abnormalities and co-syndrome in patients with FAS, and warns against excessive maternal alcohol consumption during pregnancy. PMID:27422904

  9. Soyasaponin Bb Protects Rat Hepatocytes from Alcohol-Induced Oxidative Stress by Inducing Heme Oxygenase-1

    PubMed Central

    Lijie, Zhu; Ranran, Fu; Xiuying, Liu; Yutang, He; Bo, Wang; Tao, Ma

    2016-01-01

    Background: It has been known that oxidative stress induced by alcohol played a crucial role in the formation of alcoholic liver disease. Although the formation mechanisms underlying liver injury induced by alcohol still remained largely unknown, it has been considered that oxidative stress played a core role in the pathogenesis of hepatocyte damage. Objective: The aim of this study was to investigate the effects of soyasaponin Bb (Ss-Bb) on oxidative stress in alcohol-induced rat hepatocyte injury. Results: It has been shown that the administration of Ss-Bb could significantly restore antioxidant activity in BRL 3A cells. Moreover, the impaired liver function and morphology changes resulting from ethanol exposure were improved by Ss-Bb treatment. Treatment with a pharmacological inhibitor of haem oxygenase-1 (HO-1) indicated a critical role of HO-1 in mediating the protective role. Finally, we found that pretreatment with Ss-Bb to ethanol exposure cells increased the expression level of HO-1. Conclusion: It was suggested that Ss-Bb may protect against alcohol-induced hepatocyte injury through ameliorating oxidative stress, and the induction of HO-1 was an important protective mechanism. SUMMARY Effects of soyasaponin Bb was investigated on oxidative stress in rat hepatocytesCell viability and antioxidant capacities were evaluated to determine the effectsThe expression level of HO-1 was measured to reveal the proptective mechanisms PMID:27867273

  10. Reducing Youth Exposure to Alcohol Ads: Targeting Public Transit

    PubMed Central

    2008-01-01

    Underage drinking is a major public health problem. Youth drink more heavily than adults and are more vulnerable to the adverse effects of alcohol. Previous research has demonstrated the connection between alcohol advertising and underage drinking. Restricting outdoor advertising in general and transit ads in particular, represents an important opportunity to reduce youth exposure. To address this problem, the Marin Institute, an alcohol industry watchdog group in Northern California, conducted a survey of alcohol ads on San Francisco bus shelters. The survey received sufficient media attention to lead the billboard company, CBS Outdoor, into taking down the ads. Marin Institute also surveyed the 25 largest transit agencies; results showed that 75 percent of responding agencies currently have policies that ban alcohol advertising. However, as the experience in San Francisco demonstrated, having a policy on paper does not necessarily mean it is being followed. Communities must be diligent in holding accountable government officials, the alcohol industry, and the media companies through which advertising occurs. PMID:18389374

  11. Circadian Modulation of Alcohol-Induced Sedation and Recovery in Male and Female Drosophila.

    PubMed

    De Nobrega, Aliza K; Lyons, Lisa C

    2016-04-01

    Delineating the factors that affect behavioral and neurological responses to alcohol is critical to facilitate measures for preventing or treating alcohol abuse. The high degree of conserved molecular and physiological processes makes Drosophila melanogaster a valuable model for investigating circadian interactions with alcohol-induced behaviors and examining sex-specific differences in alcohol sensitivity. We found that wild-type Drosophila exhibited rhythms in alcohol-induced sedation under light-dark and constant dark conditions with considerably greater alcohol exposure necessary to induce sedation during the late (subjective) day and peak sensitivity to alcohol occurring during the late (subjective) night. The circadian clock also modulated the recovery from alcohol-induced sedation with flies regaining motor control significantly faster during the late (subjective) day. As predicted, the circadian rhythms in sedation and recovery were absent in flies with a mutation in the circadian gene period or arrhythmic flies housed in constant light conditions. Flies lacking a functional circadian clock were more sensitive to the effects of alcohol with significantly longer recovery times. Similar to other animals and humans, Drosophila exhibit sex-specific differences in alcohol sensitivity. We investigated whether the circadian clock modulated the rhythms in the loss-of-righting reflex, alcohol-induced sedation, and recovery differently in males and females. We found that both sexes demonstrated circadian rhythms in the loss-of-righting reflex and sedation with the differences in alcohol sensitivity between males and females most pronounced during the late subjective day. Recovery of motor reflexes following alcohol sedation also exhibited circadian modulation in male and female flies, although the circadian clock did not modulate the difference in recovery times between the sexes. These studies provide a framework outlining how the circadian clock modulates alcohol-induced

  12. Circadian modulation of alcohol-induced sedation and recovery in male and female Drosophila

    PubMed Central

    De Nobrega, Aliza K.; Lyons, Lisa C.

    2016-01-01

    Delineating the factors that affect behavioral and neurological responses to alcohol is critical to facilitate measures for preventing or treating alcohol abuse. The high degree of conserved molecular and physiological processes make Drosophila melanogaster a valuable model for investigating circadian interactions with alcohol-induced behaviors and examining sex-specific differences in alcohol sensitivity. We found that wild-type Drosophila exhibit rhythms in alcohol-induced sedation under light-dark and constant dark conditions with considerably greater alcohol exposure necessary to induce sedation during the late (subjective) day and peak sensitivity to alcohol occurring during the late (subjective) night. The circadian clock also modulated the recovery from alcohol-induced sedation with flies regaining motor control significantly faster during the late (subjective) day. As predicted, the circadian rhythms in sedation and recovery were absent in flies with a mutation in the circadian gene period or arrhythmic flies housed in constant light conditions. Flies lacking a functional circadian clock were more sensitive to the effects of alcohol with significantly longer recovery times. Similar to other animals and humans, Drosophila exhibit sex-specific differences in alcohol sensitivity. We investigated whether the circadian clock modulated the rhythms in the Loss-of-Righting Reflex, alcohol-induced sedation, and recovery differently in males and females. We found that both sexes demonstrate circadian rhythms in the Loss-of-Righting Reflex and sedation with the differences in alcohol sensitivity between males and females most pronounced during the late subjective day. Recovery of motor reflexes following alcohol sedation also exhibited circadian modulation in male and female flies, although the circadian clock did not modulate the difference in recovery times between the sexes. These studies provide a framework outlining how the circadian clock modulates alcohol-induced

  13. Fetal alcohol exposure and mammary tumorigenesis in offspring: role of the estrogen and insulin-like growth factor systems.

    PubMed

    Cohick, Wendie S; Crismale-Gann, Catina; Stires, Hillary; Katz, Tiffany A

    2015-01-01

    Fetal alcohol spectrum disorders affect a significant number of live births each year, indicating that alcohol consumption during pregnancy is an important public health issue. Environmental exposures and lifestyle choices during pregnancy may affect the offspring's risk of disease in adulthood, leading to the idea that a woman's risk of breast cancer may be pre-programmed prior to birth. Exposure of pregnant rats to alcohol increases tumorigenesis in the adult offspring in response to mammary carcinogens. The estrogen and insulin-like growth factor (IGF-I) axes occupy central roles in normal mammary gland development and breast cancer. 17-β estradiol (E2) and IGF-I synergize to regulate formation of terminal end buds and ductal elongation during pubertal development. The intracellular signaling pathways mediated by the estrogen and IGF-I receptors cross-talk at multiple levels through both genomic and non-genomic mechanisms. Several components of the E2 and IGF-I systems are altered in early development in rat offspring exposed to alcohol in utero, therefore, these changes may play a role in the enhanced susceptibility to mammary carcinogens observed in adulthood. Alcohol exposure in utero induces a number of epigenetic alterations in non-mammary tissues in the offspring and other adverse in utero exposures induce epigenetic modifications in the mammary gland. Future studies will determine if fetal alcohol exposure can induce epigenetic modifications in genes that regulate E2/IGF action at key phases of mammary development, ultimately leading to changes in susceptibility to carcinogens.

  14. Alcohol Environment, Perceived Safety, and Exposure to Alcohol, Tobacco, and Other Drugs in Early Adolescence

    PubMed Central

    Milam, AJ; Furr-Holden, CDM; Bradshaw, CP; Webster, DW; Cooley-Strickland, MC; Leaf, PJ

    2013-01-01

    This study examined the association between the count of alcohol outlets around children's homes and opportunities to use alcohol, tobacco, and other drugs (ATOD) during pre-adolescence. Data were collected in 2007 from 394 Baltimore City children aged 8-13 (86% African American). Participants' residential address and alcohol outlet data were geocoded with quarter mile (i.e., walking distance) buffers placed around each participant's home to determine the number of outlets within walking distance. The unadjusted logistic regression models revealed that each unit increase in the number of alcohol outlets was associated with a 14% increase in the likelihood of children seeing people selling drugs (OR=1.14, p=.04) and a 15% increase in the likelihood of seeing people smoking marijuana (OR=1.15, p<.01). After adjusting for neighborhood physical disorder, the relationship between alcohol outlets and seeing people selling drugs and seeing people smoking marijuana was fully attenuated. These results suggest that alcohol outlets are one aspect of the larger environmental context that is related to ATOD exposure in children. Future studies should examine the complex relationship between neighborhood physical disorder and the presence of alcohol outlets. PMID:25125766

  15. Microbiota protects mice against acute alcohol-induced liver injury

    PubMed Central

    Chen, Peng; Miyamoto, Yukiko; Mazagova, Magdalena; Lee, Kuei-Chuan; Eckmann, Lars; Schnabl, Bernd

    2015-01-01

    Background Chronic alcohol abuse is associated with intestinal bacterial overgrowth, increased intestinal permeability, and translocation of microbial products from the intestine to the portal circulation and liver. Translocated microbial products contribute to experimental alcoholic liver disease. Aim To investigate the physiological relevance of the intestinal microbiota in alcohol-induced liver injury. Methods We subjected germ-free and conventional C57BL/6 mice to a model of acute alcohol exposure that mimics binge drinking. Results Germ-free mice showed significantly greater liver injury and inflammation after oral gavage of ethanol compared with conventional mice. In parallel, germ-free mice exhibited increased hepatic steatosis and upregulated expression of genes involved in fatty acid and triglyceride synthesis compared with conventional mice after acute ethanol administration. The absence of microbiota was also associated with increased hepatic expression of ethanol metabolizing enzymes, which led to faster ethanol elimination from the blood and lower plasma ethanol concentrations. Intestinal levels of ethanol metabolizing genes showed regional expression differences, and were overall higher in germ-free relative to conventional mice. Conclusion Our findings indicate that absence of the intestinal microbiota increases hepatic ethanol metabolism and the susceptibility to binge-like alcohol drinking. PMID:26556636

  16. Prenatal alcohol exposure alters the patterns of facial asymmetry.

    PubMed

    Klingenberg, C P; Wetherill, L; Rogers, J; Moore, E; Ward, R; Autti-Rämö, I; Fagerlund, A; Jacobson, S W; Robinson, L K; Hoyme, H E; Mattson, S N; Li, T K; Riley, E P; Foroud, T

    2010-01-01

    Directional asymmetry, the systematic differences between the left and right body sides, is widespread in human populations. Changes in directional asymmetry are associated with various disorders that affect craniofacial development. Because facial dysmorphology is a key criterion for diagnosing fetal alcohol syndrome (FAS), the question arises whether in utero alcohol exposure alters directional asymmetry in the face. Data on the relative position of 17 morphologic landmarks were obtained from facial scans of children who were classified as either FAS or control. Shape data obtained from the landmarks were analyzed with the methods of geometric morphometrics. Our analyses showed significant directional asymmetry of facial shape, consisting primarily of a shift of midline landmarks to the right and a displacement of the landmarks around the eyes to the left. The asymmetry of FAS and control groups differed significantly and average directional asymmetry was increased in those individuals exposed to alcohol in utero. These results suggest that the developmental consequences of fetal alcohol exposure affect a wide range of craniofacial features in addition to those generally recognized and used for diagnosis of FAS.

  17. Alcohol-induced facial dysmorphology in C57BL/6 mouse models of fetal alcohol spectrum disorder.

    PubMed

    Anthony, Bruce; Vinci-Booher, Sophia; Wetherill, Leah; Ward, Richard; Goodlett, Charles; Zhou, Feng C

    2010-01-01

    Alcohol consumption during pregnancy causes fetal alcohol spectrum disorder (FASD), which includes a range of developmental deficits. Fetal alcohol syndrome is the most severe form of FASD and can be diagnosed with pathognomonic facial features such as a smooth philtrum, short palpebral fissure, and thin upper vermilion. However, many children with developmental damage because of prenatal alcohol exposure exhibit none, or only a subset, of the above features, making diagnosis difficult. This study explored novel analyses to quantify the effect of a known dose of alcohol on specific facial measurements in substrains C57BL/B6J (B6J) and C57BL/6NHsd (B6N) mice. Mouse dams were provided alcohol (Alc) consisting of 4.8% (vol/vol) alcohol in a liquid diet for 16 days prepregnancy and chow and water diet during mating, and then the alcohol liquid diet was reinstated on gestational days 7 (E7) to gestational day 17 (E17). Treatment controls included a pair-fed (PF) group given matched volumes of an alcohol-free liquid diet made isocalorically and a group given ad lib access to lab chow and water (Chow). Maternal diet intake (Alc and PF), blood alcohol concentrations (BACs), embryo weights, and 15 morphometric facial measurements for E17 embryos were analyzed. B6N dams drank more alcohol during pregnancy and generated higher BAC than B6J dams. Both the Alc and PF treatments induced significant reductions in embryo weights relative to Chow in both substrains. Alcohol treatments produced significant changes, relative to controls, in 4 of the 15 facial measures for the B6N substrain but only in two measures for the B6J substrain. Discriminant analysis demonstrated successful classification of the alcohol-exposed versus nonalcohol-exposed B6N embryos, with a high sensitivity of 86%, specificity 80%, and overall classification (total correct 83%), whereas B6J mice yielded sensitivity of 80%, specificity 78%, and overall correct classification in 79%. In addition, B6N mice showed

  18. Alcohol induced changes in phosphoinositide signaling system in rat brain

    SciTech Connect

    Pandey, S.; Piano, M.; Schwertz, D.; Davis, J.; Pandey, G. )

    1991-03-11

    Agonist-induced phosphoinositide break down functions as a signal generating system in a manner similar to the C-AMP system. In order to examine if the changes produced by chronic ethanol treatment on membrane lipid composition and metabolism effect the cellular functions of the neuron, the authors have examined the effect of chronic ethanol exposure on norepinephrine (NE) serotonin (5HT) and calcium ionophore (CI) stimulated phosphoinositide (PI) hydrolysis in rat cortical slices. Rats were maintained on liber-decarli diet alcohol and control liquid diet containing isocaloric sucrose substitute for two months. They were then sacrificed and brain was removed for determination of PI turnover. 5HT stimulated {sup 3}H- inositol monophosphate ({sup 3}H-IPI) formation was significantly lower in the cortex of alcohol treated rats as compared to control rats. However, neither CI nor NE stimulated IP1 formation was significantly different from control rats. The results thus indicate that chronic exposure to ethanol decreases 5HT induced PI breakdown in rat cortex. In order to examine if this decrease is related to a decrease in 5HT2 receptors, or decreased in coupling of receptor to the effector pathway, the authors are currently determining the number and affinity of 5HT2 receptors in alcohol treated rats.

  19. Prenatal alcohol exposure and miscarriage, stillbirth, preterm delivery, and sudden infant death syndrome.

    PubMed

    Bailey, Beth A; Sokol, Robert J

    2011-01-01

    In addition to fetal alcohol syndrome and fetal alcohol spectrum disorders, prenatal alcohol exposure is associated with many other adverse pregnancy and birth outcomes. Research suggests that alcohol use during pregnancy may increase the risk of miscarriage, stillbirth, preterm delivery, and sudden infant death syndrome. This research has some inherent difficulties, such as the collection of accurate information about alcohol consumption during pregnancy and controlling for comorbid exposures and conditions. Consequently, attributing poor birth outcomes to prenatal alcohol exposure is a complicated and ongoing task, requiring continued attention to validated methodology and to identifying specific biological mechanisms.

  20. Alcohol-induced protein hyperacetylation: Mechanisms and consequences

    PubMed Central

    Shepard, Blythe D; Tuma, Pamela L

    2009-01-01

    Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein hyperacetylation. This reversible, post-translational modification on the epsilon-amino groups of lysine residues has been shown to modulate multiple, diverse cellular processes ranging from transcriptional activation to microtubule stability. Thus, alcohol-induced protein hyperacetylation likely leads to major physiological consequences that contribute to alcohol-induced hepatotoxicity. Lysine acetylation is controlled by the activities of two opposing enzymes, histone acetyltransferases and histone deacetylases. Currently, efforts are aimed at determining which enzymes are responsible for the increased acetylation of specific substrates. However, the greater challenge will be to determine the physiological ramifications of protein hyperacetylation and how they might contribute to the progression of liver disease. In this review, we will first list and discuss the proteins known to be hyperacetylated in the presence of ethanol. We will then describe what is known about the mechanisms leading to increased protein acetylation and how hyperacetylation may perturb hepatic function. PMID:19291822

  1. Chronic alcohol exposure alters transcription broadly in a key integrative brain nucleus for homeostasis: the nucleus tractus solitarius.

    PubMed

    Covarrubias, Maria Yolanda; Khan, Rishi L; Vadigepalli, Rajanikanth; Hoek, Jan B; Schwaber, James S

    2005-12-14

    Chronic exposure to alcohol modifies physiological processes in the brain, and the severe symptoms resulting from sudden removal of alcohol from the diet indicate that these modifications are functionally important. We investigated the gene expression patterns in response to chronic alcohol exposure (21-28 wk) in the rat nucleus tractus solitarius (NTS), a brain nucleus with a key integrative role in homeostasis and cardiorespiratory function. Using methods and an experimental design optimized for detecting transcriptional changes less than twofold, we found 575 differentially expressed genes. We tested these genes for significant associations with physiological functions and signaling pathways using Gene Ontology terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, respectively. Chronic alcohol exposure resulted in significant NTS gene regulation related to the general processes of synaptic transmission, intracellular signaling, and cation transport as well as specific neuronal functions including plasticity and seizure behavior that could be related to alcohol withdrawal symptoms. The differentially expressed genes were also significantly enriched for enzymes of lipid metabolism, glucose metabolism, oxidative phosphorylation, MAP kinase signaling, and calcium signaling pathways from KEGG. Intriguingly, many of the genes we found to be differentially expressed in the NTS are known to be involved in alcohol-induced oxidative stress and/or cell death. The study provides evidence of very extensive alterations of physiological gene expression in the NTS in the adapted state to chronic alcohol exposure.

  2. Moderate prenatal alcohol exposure alters behavior and neuroglial parameters in adolescent rats.

    PubMed

    Brolese, Giovana; Lunardi, Paula; Broetto, Núbia; Engelke, Douglas S; Lírio, Franciane; Batassini, Cristiane; Tramontina, Ana Carolina; Gonçalves, Carlos-Alberto

    2014-08-01

    Alcohol consumption by women during gestation has become increasingly common. Although it is widely accepted that exposure to high doses of ethanol has long-lasting detrimental effects on brain development, the case for moderate doses is underappreciated, and benchmark studies have demonstrated structural and behavioral defects associated with moderate prenatal alcohol exposure in humans and animal models. This study aimed to investigate the influence of in utero exposure to moderate levels of ethanol throughout pregnancy on learning/memory, anxiety parameters and neuroglial parameters in adolescent offspring. Female rats were exposed to an experimental protocol throughout gestation up to weaning. After mating, the dams were divided into three groups and treated with only water (control), non-alcoholic beer (vehicle) or 10% (vv) beer solution (moderate prenatal alcohol exposure - MPAE). Adolescent male offspring were subjected to the plus-maze discriminative avoidance task to evaluate learning/memory and anxiety-like behavior. Hippocampi were dissected and slices were obtained for immunoquantification of GFAP, NeuN, S100B and the NMDA receptor. The MPAE group clearly presented anxiolytic-like behavior, even though they had learned how to avoid the aversive arm. S100B protein was increased in the cerebrospinal fluid (CSF) in the group treated with alcohol, and alterations in GFAP expression were also shown. This study indicates that moderate ethanol doses administered during pregnancy could induce anxiolytic-like effects, suggesting an increase in risk-taking behavior in adolescent male offspring. Furthermore, the data show the possibility that glial cells are involved in the altered behavior present after prenatal ethanol treatment.

  3. Chronic and acute alcohol administration induced neurochemical changes in the brain: comparison of distinct zebrafish populations.

    PubMed

    Chatterjee, Diptendu; Shams, Soaleha; Gerlai, Robert

    2014-04-01

    The zebrafish is increasingly utilized in the analysis of the effects of ethanol (alcohol) on brain function and behavior. We have shown significant population-dependent alcohol-induced changes in zebrafish behavior and have started to analyze alterations in dopaminergic and serotoninergic responses. Here, we analyze the effects of alcohol on levels of selected neurochemicals using a 2 × 3 (chronic × acute) between-subject alcohol exposure paradigm randomized for two zebrafish populations, AB and SF. Each fish first received the particular chronic treatment (0 or 0.5 vol/vol% alcohol) and subsequently the acute exposure (0, 0.5 or 1.0% alcohol). We report changes in levels of dopamine, DOPAC, serotonin, 5HIAA, glutamate, GABA, aspartate, glycine and taurine as quantified from whole brain extracts using HPLC. We also analyze monoamine oxidase and tyrosine hydroxylase enzymatic activity. The results demonstrate that compared to SF, AB is more responsive to both acute alcohol exposure and acute alcohol withdrawal at the level of neurochemistry, a finding that correlates well with prior behavioral observations and one which suggests the involvement of genes in the observed alcohol effects. We discuss correlations between the current results and prior behavioral findings, and stress the importance of characterization of zebrafish strains for future behavior genetic and psychopharmacology studies.

  4. Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation.

    PubMed

    Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P; Zhou, Feng C

    2009-10-01

    Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10, and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p<0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes in

  5. The role of kappa opioid receptors in stress-induced reinstatement of alcohol seeking in rats

    PubMed Central

    Funk, Douglas; Coen, Kathleen; Lê, A D

    2014-01-01

    Introduction Stress is related to heavy alcohol use and relapse in alcoholics. Using the reinstatement model, we have shown that corticotropin-releasing factor (CRF) underlies stress-induced relapse to alcohol seeking in laboratory rodents. Little is known about how other neurotransmitters interact with CRF in these effects. Dynorphin and its receptor (kappa opioid receptor, KOR) are involved in stress responses and in alcohol seeking. KOR and CRF receptors (CRF R) may interact in the production of stress-related behaviors but it is not known whether this interaction is involved in reinstatement of alcohol seeking. Methods Male Long Evans rats were trained to self-administer alcohol (12% w/v). After extinction of responding, we determined the effects of the KOR agonist, U50,488 (2.5, 5 mg/kg) on reinstatement of alcohol seeking, and their sensitivity to the selective KOR antagonist nor-binaltorphimine dihydrochloride (nor-BNI) (10 mg/kg) administered at different times before U50,488. We then examined the effects of nor-BNI on reinstatement induced by the stressor yohimbine (1.25 mg/kg) and on reinstatement induced by exposure to alcohol-associated cues. Finally, we determined whether CRF R1 blockade with antalarmin (10, 20 mg/kg) attenuates alcohol seeking induced by U50,488. Results U50,488 reinstated alcohol seeking. Prior treatment with nor-BNI 2, but not 24 h before administration of U50,488 or yohimbine blocked reinstatement induced by these drugs. Cue-induced reinstatement was blocked by nor-BNI administered 2 h prior to testing. Finally, U50,488-induced reinstatement was blocked by antalarmin. Conclusions These data further support a role for KOR in reinstatement of alcohol seeking under nonstress and stressful conditions and that KOR and CRF R interact in these effects. PMID:24944865

  6. Effect of alcohol exposure on fetal brain development

    NASA Astrophysics Data System (ADS)

    Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

    2013-02-01

    Alcohol consumption during pregnancy can be severely damage to the brain development in fetuses. This study investigates the effects of maternal ethanol consumption on brain development in mice embryos. Pregnant mice at gestational day 12.5 were intragastrically gavaged with ethanol (3g/Kg bwt) twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and fixed in 4% paraformaldehyde and imaged using a swept-source optical coherence tomography (SSOCT) system. 3D images of the mice embryo brain were obtained and the volumes of the left and right ventricles of the brain were measured. The average volumes of the left and the right volumes of 5 embryos each alcohol-exposed and control embryos were measured to be 0.35 and 0.15 mm3, respectively. The results suggest that the left and right ventricle volumes of brain are much larger in the alcohol-exposed embryos as compared to control embryos indicating alcohol-induced developmental delay.

  7. Light alcohol intake during adolescence induces alcohol addiction in a neurodevelopmental model of schizophrenia.

    PubMed

    Jeanblanc, Jérôme; Balguerie, Kevin; Coune, Fabien; Legastelois, Rémi; Jeanblanc, Virginie; Naassila, Mickaël

    2015-05-01

    Schizophrenia is a mental disorder characterized by a series of positive, negative or cognitive symptoms but with also the particularity of exhibiting a high rate of co-morbid use of drugs of abuse. While more than 80% of schizophrenics are smokers, the second most consumed drug is alcohol, with dramatic consequences on frequency and intensity of psychotic episodes and on life expectancy. Here we investigated the impact of light alcohol intake during adolescence on the subsequent occurrence of alcohol addiction-like behavior in neonatal ventral hippocampal lesion (NVHL) rats, a neurodevelopmental model of schizophrenia. Our findings demonstrated an increased liability to addictive behaviors in adult NVHL rats after voluntary alcohol intake during adolescence. NVHL rats displayed several signs of alcohol use disorder such as a loss of control over alcohol intake and high motivation to consume alcohol, associated with a higher resistance to extinction. In addition, once NVHL rats relapsed, they maintained higher drinking levels than controls. We finally showed that the anti-addictive drug naltrexone is efficient in reducing excessive alcohol intake in NVHL rats. Our results are in accordance with epidemiological studies underlying the particular vulnerability to alcohol addiction after adolescent exposure to alcohol and highlight the fact that schizophrenic subjects may be particularly at risk even after light alcohol consumption. Based on these results, it seems particularly relevant to prevent early onset of alcohol use in at-risk subjects and thus to reduce the incidence of co-morbid alcohol abuse in psychotic patients.

  8. 99HRT Effects of Chronic Alcohol Exposure on Kainate Receptor-Mediated Neurotransmission in the Hippocampus

    DTIC Science & Technology

    2003-09-01

    NEUROTRANSMITTERS, * ELECTROPHYSIOLOGY , *DRUG ABUSE, *ETHANOLS, VAPORS, SENSITIVITY, LONG RANGE(TIME), EXPOSURE(PHYSIOLOGY), CENTRAL NERVOUS SYSTEM, RECEPTOR SITES(PHYSIOLOGY), ALCOHOLS, HIPPOCAMPUS, CEREBELLUM.

  9. Discriminating the Effects of Prenatal Alcohol Exposure From Other Behavioral and Learning Disorders

    PubMed Central

    Coles, Claire D.

    2011-01-01

    Fetal alcohol syndrome and fetal alcohol spectrum disorders are underdiagnosed in general treatment settings. Among the factors involved in identifying the effects of prenatal alcohol exposure are (1) the evidence for prenatal alcohol exposure; (2) the effects of the postnatal, caregiving environment; (3) comorbidities; and (4) differential diagnosis, which includes identifying the neurodevelopmental effects of alcohol and discriminating these effects from those characterizing other conditions. This article reviews findings on the neurodevelopmental effects of prenatal alcohol exposure, including learning and memory, motor and sensory/motor effects, visual/spatial skills, and executive functioning and effortful control. Encouraging clinicians to discriminate the effects of prenatal alcohol exposure from other conditions may require more education and training but ultimately will improve outcomes for affected children. PMID:23580040

  10. Fetal Alcohol Exposure Reduces Dopamine Receptor D2 and Increases Pituitary Weight and Prolactin Production via Epigenetic Mechanisms

    PubMed Central

    Gangisetty, Omkaram; Wynne, Olivia; Jabbar, Shaima; Nasello, Cara; Sarkar, Dipak K.

    2015-01-01

    Recent evidence indicated that alcohol exposure during the fetal period increases the susceptibility to tumor development in mammary and prostate tissues. Whether fetal alcohol exposure increases the susceptibility to prolactin-producing tumor (prolactinoma) development in the pituitary was studied by employing the animal model of estradiol-induced prolactinomas in Fischer 344 female rats. We employed an animal model of fetal alcohol exposure that simulates binge alcohol drinking during the first two trimesters of human pregnancy and involves feeding pregnant rats with a liquid diet containing 6.7% alcohol during gestational day 7 to day 21. Control rats were pair-fed with isocaloric liquid diet or fed ad libitum with rat chow diet. Adult alcohol exposed and control female offspring rats were used in this study on the day of estrus or after estrogen treatment. Results show that fetal alcohol-exposed rats had increased levels of pituitary weight, pituitary prolactin (PRL) protein and mRNA, and plasma PRL. However, these rats show decreased pituitary levels of dopamine D2 receptor (D2R) mRNA and protein and increased pituitary levels of D2R promoter methylation. Also, they show elevated pituitary mRNA levels of DNA methylating genes (DNMT1, DNMT3b, MeCP2) and histone modifying genes (HDAC2, HDAC4, G9a). When fetal alcohol exposed rats were treated neonatally with a DNA methylation inhibitor 5-Aza deoxycytidine and/or a HDAC inhibitor trichostatin-A their pituitary D2R mRNA, pituitary weights and plasma PRL levels were normalized. These data suggest that fetal alcohol exposure programs the pituitary to increase the susceptibility to the development of prolactinomas possibly by enhancing the methylation of the D2R gene promoter and repressing the synthesis and control of D2R on PRL-producing cells. PMID:26509893

  11. Prenatal Exposure to Drugs/Alcohol: Characteristics and Educational Implications of Fetal Alcohol Syndrome and Cocaine/Polydrug Effects.

    ERIC Educational Resources Information Center

    Soby, Jeanette M.

    This book presents the characteristics of children affected by prenatal drug exposure, fetal alcohol syndrome, fetal alcohol effects, and fetal cocaine/polydrug effects. It outlines incidence, service needs, prevention, and identification. The medical literature on the physical, cognitive, and behavioral characteristics of this population is…

  12. Alarming prevalence of fetal alcohol exposure in a Mediterranean city.

    PubMed

    Garcia-Algar, Oscar; Kulaga, Vivan; Gareri, Joey; Koren, Gideon; Vall, Oriol; Zuccaro, Piergiorgio; Pacifici, Roberta; Pichini, Simona

    2008-04-01

    The prevalence of gestational ethanol exposure and subsequent fetal exposure has been assessed in a cohort of mother-infant dyads in a Mediterranean city (Barcelona, Spain) by meconium analysis of fatty acid ethyl esters (FAEEs) after showing in this population a high prevalence of meconium opiates (8.7%), cocaine (4.4%), and cannabis (5.3%). Of the 353 meconium samples analyzed for FAEEs, 159 (45%) contained a total amount of seven FAEEs equal or above 2 nmol/g meconium, the cutoff internationally accepted to differentiate heavy maternal alcohol consumption during pregnancy from occasional use or no use at all. No parental sociodemographic differences or maternal features differentiated exposed from unexposed newborns. The prevalence of gestational consumption of ethanol was similar between women using and not using drugs of abuse during pregnancy (45.7% and 44.7% of samples with total FAEEs equal or higher than 2 nmol/g meconium, respectively). Meconium samples from newborns exposed in utero to ethanol, and positive for at least one illicit drug (cocaine, opiates, or cannabis), had total FAEEs and five of nine individual FAEEs statistically higher than the meconium samples that were negative for the most frequently used illicit drugs of abuse. Among the most prevalent FAEEs, oleic acid ethyl ester showed the best correlation to total FAEE concentration followed by palmitoleic acid ethyl ester . This study, which highlights a 45% ethanol consumption during pregnancy in a low socioeconomic status cohort, may serve as an eye opener for Europeans that gestational alcohol exposure is not endemic only in areas outside of Europe.

  13. Ocular deficits associated with alcohol exposure during zebrafish development.

    PubMed

    Dlugos, Cynthia A; Rabin, Richard A

    2007-06-01

    Approximately 90% of fetal alcohol syndrome cases are accompanied by ocular abnormalities. The zebrafish (Danio rerio) is a well-known developmental model that provides an opportunity for better understanding the histological and cytological effects of developmental exposure to ethanol on the vertebrate eye. The purpose of the present study was to determine the gross, microscopic, and ultrastructual effects of developmental exposure to ethanol in the zebrafish model. Eggs were obtained from WT outbred zebrafish and exposed to 0%, 0.1%, 0.2%, 0.4%, 0.5%, or 1.0% (v/v) ethanol to assess viability and the effect of dose and duration of exposure on eye size. Light and electron microscopy were performed on ethanol-treated and control larvae. Results showed that ethanol treatment decreased viability by about 20% at concentrations of 0.1-0.5% ethanol and by 50% at 1.0% ethanol. Ethanol-related decreases in eye size were recorded at 6 days postfertilization (dpf) and were dose dependent. There were significant decreases in the volumes of the photoreceptor, inner nuclear, and ganglionic layers and in the lens of 9 dpf ethanol-exposed compared with control larvae. Ultrastructural examination showed signs of developmental lags in the ethanol-treated fish as well as abnormal retinal apoptosis in the 6 dpf ethanol-treated larvae compared with their controls. These results demonstrate that the developing zebrafish eye is sensitive to perturbation with ethanol and displays some of the eye deficits present in fetal alcohol syndrome.

  14. Reversible loss of reproductive fitness in zebrafish on chronic alcohol exposure.

    PubMed

    Dewari, Pooran Singh; Ajani, Funmilola; Kushawah, Gopal; Kumar, Damera Santhosh; Mishra, Rakesh K

    2016-02-01

    Alcoholism is one of the most prevalent diseases in society and causes significant health and social problems. Alcohol consumption by pregnant women is reported to cause adverse effects on the physical and psychological growth of the fetus. However, the direct effect of chronic alcohol consumption on reproductive fitness has not been tested. In recent years, the zebrafish (Danio rerio) has emerged as a versatile model system to study the effects of alcohol on behavior and embryonic development. We utilized the zebrafish model system to address the effect of chronic alcohol exposure (0.5% alcohol in the holding tank for 9 weeks) on reproductive capacity. We found a dramatic decrease in fecundity, measured by counting the number of eggs laid, when at least one of the parents is subject to chronic alcohol exposure. Interestingly, a 9-week alcohol withdrawal program completely restored the reproductive capacity of the treated subjects. In agreement with observations on fecundity, the chronic alcohol exposure leads to increased anxiety, as measured by the novel-tank diving assay. Conversely, the withdrawal program diminished heightened anxiety in alcohol-exposed subjects. Our results highlight the adverse effects of chronic alcohol exposure on the reproductive capacity of both males and females, and underscore the utility of the zebrafish model system to understand the biology of chronic alcoholism.

  15. Embryonic alcohol exposure promotes long-term effects on cerebral glutamate transport of adult zebrafish.

    PubMed

    Baggio, Suelen; Mussulini, Ben Hur; de Oliveira, Diogo Losch; Zenki, Kamila Cagliari; Santos da Silva, Emerson; Rico, Eduardo Pacheco

    2017-01-01

    Ethanol is a widely consumed substance throughout the world. During development it can substantially damage the human fetus, whereas the developing brain is particularly vulnerable. The brain damage induced by prenatal alcohol exposure may lead to a variety of long-lasting behavioral and neurochemical problems. However, there are no data concerning the effects of developmental ethanol exposure on the glutamatergic system, where extracellular glutamate acts as signaling molecule. Here we investigated the effect of ethanol exposure for 2h (concentrations of 0.0%, 0.1%, 0.25%, 0.50%, and 1.00%) in embryos at 24h post-fertilization (hpf) by measuring the functionality of glutamate transporters in the brain of adult (4 months) zebrafish. However, ethanol 0.1%, 0.25% and 0.50% decreased transport of glutamate to 81.96%, 60.65% and 45.91% respectively, when compared with the control group. Interestingly, 1.00% was able to inhibit the transport activity to 68.85%. In response to the embryonic alcohol exposure, we found impairment in the function of cerebral glutamate transport in adult fish, contributing to long-term alteration in the homeostasis glutamatergic signaling.

  16. Diminished adrenocorticotropin response to insulin-induced hypoglycemia in nondepressed, actively drinking male alcoholics.

    PubMed

    Berman, J D; Cook, D M; Buchman, M; Keith, L D

    1990-09-01

    Although changes in hypothalamic-pituitary-adrenal axis function have frequently been reported in alcoholics, the majority of studies have used recently detoxified subjects in whom abstinence phenomena and clinical depression may contribute to observed stress axis alterations. To isolate the primary effects of alcohol dependence on the stress axis, the ACTH and cortisol responses to insulin-induced hypoglycemia were measured in seven actively drinking male alcoholics recruited from the general public through a newspaper advertisement along with eight age-matched male controls. The alcoholic subjects met current American Psychiatric Association diagnostic criteria for alcohol dependence, were stably employed, and had no concurrent psychiatric disorders, cognitive impairment, or psychometric evidence of depression. While relatively young (30.0 yr; range, 22-48 yr), they had lengthy histories of alcohol-related problems (11.9 yr; range, 5-30 yr). Insulin administration resulted in similar nadirs in blood sugar in both alcoholic and control groups. However, the plasma ACTH response was markedly blunted in the alcoholics (P = 0.040, by Mann-Whitney U test). There was a nonsignificant trend toward increased cortisol levels in the alcoholic group. The findings suggest that altered hypothalamic-pituitary-adrenal axis function in alcoholics is a primary results of chronic ethanol exposure rather than a confounding effect of clinical depression or recent detoxification.

  17. Fibroblast growth factor 21 deficiency exacerbates chronic alcohol-induced hepatic steatosis and injury

    PubMed Central

    Liu, Yanlong; Zhao, Cuiqing; Xiao, Jian; Liu, Liming; Zhang, Min; Wang, Cuiling; Wu, Guicheng; Zheng, Ming-Hua; Xu, Lan-Man; Chen, Yong-Ping; Mohammadi, Moosa; Chen, Shao-Yu; Cave, Matthew; McClain, Craig; Li, Xiaokun; Feng, Wenke

    2016-01-01

    Fibroblast growth factor 21 (FGF21) is a hepatokine that regulates glucose and lipid metabolism in the liver. We sought to determine the role of FGF21 in hepatic steatosis in mice exposed to chronic alcohol treatment and to discern underlying mechanisms. Male FGF21 knockout (FGF21 KO) and control (WT) mice were divided into groups that were fed either the Lieber DeCarli diet containing 5% alcohol or an isocaloric (control) diet for 4 weeks. One group of WT mice exposed to alcohol received recombinant human FGF21 (rhFGF21) in the last 5 days. Liver steatosis and inflammation were assessed. Primary mouse hepatocytes and AML-12 cells were incubated with metformin or rhFGF21. Hepatic genes and the products involved in in situ lipogenesis and fatty acid β-oxidation were analyzed. Alcohol exposure increased circulating levels and hepatic expression of FGF21. FGF21 depletion exacerbated alcohol-induced hepatic steatosis and liver injury, which was associated with increased activation of genes involved in lipogenesis mediated by SREBP1c and decreased expression of genes involved in fatty acid β-oxidation mediated by PGC1α. rhFGF21 administration reduced alcohol-induced hepatic steatosis and inflammation in WT mice. These results reveal that alcohol-induced FGF21 expression is a hepatic adaptive response to lipid dysregulation. Targeting FGF21 signaling could be a novel treatment approach for alcoholic steatohepatitis. PMID:27498701

  18. Ethanol administration dampens the prolactin response to psychosocial stress exposure in sons of alcohol-dependent fathers.

    PubMed

    Zimmermann, Ulrich S; Buchmann, Arlette F; Spring, Constance; Uhr, Manfred; Holsboer, Florian; Wittchen, Hans-Ulrich

    2009-08-01

    Genetic predisposition and exposure to alcohol and stress increase the risk for alcoholism, possibly by forming a threefold interaction. This is suggested by various aspects of alcohol-induced stress response dampening in offspring of alcoholics. We tested whether such an interaction is also revealed by prolactin secretion, which is predominantly controlled by hypothalamic dopamine. Plasma prolactin was measured during four experimental days in 26 young males with a paternal history of alcoholism (PHA) and in 22 family history negative (FHN) controls. A public speaking stress paradigm was applied on the first 2 days, and a non-stress acoustic startle experiment on the others. Before the tests, subjects drank alcohol (0.6 g/kg) or placebo in a randomized, double-blind crossover design. During placebo experiments, prolactin levels significantly increased after stress, but not after startle, and did not differ between risk groups. Alcohol administration significantly increased prolactin before stress and during startle in both groups, did not alter stress-induced prolactin stimulation in FHN, but significantly attenuated the prolactin stress response in PHA subjects. The alcohol effects on prolactin, cortisol, and adrenocorticotropin stress response were positively interrelated with each other. These data confirm that alcohol specifically dampens the stress response in PHA but not FHN subjects. Since prolactin responses to stress alone and alcohol alone were normal in PHA, we conclude that this genetic effect is not related to altered physiology of the hypothalamic dopaminergic system, but to risk-group specific alcohol effects on hierarchically higher brain areas controlling the stress response in general.

  19. Transient activation of microglia following acute alcohol exposure in developing mouse neocortex is primarily driven by BAX-dependent neurodegeneration.

    PubMed

    Ahlers, Katelin E; Karaçay, Bahri; Fuller, Leah; Bonthius, Daniel J; Dailey, Michael E

    2015-10-01

    Fetal alcohol exposure is the most common known cause of preventable mental retardation, yet we know little about how microglia respond to, or are affected by, alcohol in the developing brain in vivo. Using an acute (single day) model of moderate (3 g/kg) to severe (5 g/kg) alcohol exposure in postnatal day (P) 7 or P8 mice, we found that alcohol-induced neuroapoptosis in the neocortex is closely correlated in space and time with the appearance of activated microglia near dead cells. The timing and molecular pattern of microglial activation varied with the level of cell death. Although microglia rapidly mobilized to contact and engulf late-stage apoptotic neurons, apoptotic bodies temporarily accumulated in neocortex, suggesting that in severe cases of alcohol toxicity the neurodegeneration rate exceeds the clearance capacity of endogenous microglia. Nevertheless, most dead cells were cleared and microglia began to deactivate within 1-2 days of the initial insult. Coincident with microglial activation and deactivation, there was a transient increase in expression of pro-inflammatory factors, TNFα and IL-1β, after severe (5 g/kg) but not moderate (3 g/kg) EtOH levels. Alcohol-induced microglial activation and pro-inflammatory factor expression were largely abolished in BAX null mice lacking neuroapoptosis, indicating that microglial activation is primarily triggered by apoptosis rather than the alcohol. Therefore, acute alcohol exposure in the developing neocortex causes transient microglial activation and mobilization, promoting clearance of dead cells and tissue recovery. Moreover, cortical microglia show a remarkable capacity to rapidly deactivate following even severe neurodegenerative insults in the developing brain.

  20. Effects of Alcohol-Induced Working Memory Decline on Alcohol Consumption and Adverse Consequences of Use

    PubMed Central

    Lechner, William V.; Day, Anne M.; Metrik, Jane; Leventhal, Adam M.; Kahler, Christopher W.

    2015-01-01

    Rationale Alcohol use appears to decrease executive function acutely in a dose dependent manner, and lower baseline executive function appears to contribute to problematic alcohol use. However, no studies, to our knowledge, have examined the relationship between individual differences in working memory (a subcomponent of executive function) after alcohol consumption and drinking behaviors and consequences. Objectives The current study assessed the relationship between drinking behavior, alcohol-related consequences, and alcohol-induced changes in working memory (as assessed by Trails Making Test-B). Method Participants recruited from the community (n = 41), 57.3% male, mean age 39.2, took part in a three-session, within-subjects, repeated-measures design. Participants were administered a placebo, 0.4 g/kg, or 0.8 g/kg dose of alcohol. Working memory, past 30 day alcohol consumption, and consequences of alcohol use were measured at baseline; working memory was measured again after each beverage administration. Results Poorer working memory after alcohol administration (controlling for baseline working memory) was significantly associated with a greater number of drinks consumed per drinking day. Additionally, we observed a significant indirect relationship between the degree of alcohol-induced working memory decline and adverse consequences of alcohol use, which was mediated through greater average drinks per drinking day. Conclusions It is possible that greater individual susceptibility to alcohol-induced working memory decline may limit one’s ability to moderate alcohol consumption as evidenced by greater drinks per drinking day, and that this results in more adverse consequences of alcohol use. PMID:26407604

  1. Social Information Processing Skills in Children with Histories of Heavy Prenatal Alcohol Exposure

    ERIC Educational Resources Information Center

    McGee, Christie L.; Bjorkquist, Olivia A.; Price, Joseph M.; Mattson, Sarah N.; Riley, Edward P.

    2009-01-01

    Based on caregiver report, children with prenatal alcohol exposure have difficulty with social functioning, but little is known about their social cognition. The current study assessed the social information processing patterns of school-age children with heavy prenatal alcohol exposure using a paradigm based on Crick and Dodge's reformulated…

  2. Neurobiology and Neurodevelopmental Impact of Childhood Traumatic Stress and Prenatal Alcohol Exposure

    ERIC Educational Resources Information Center

    Henry, Jim; Sloane, Mark; Black-Pond, Connie

    2007-01-01

    Purpose: Research reveals that prenatal alcohol exposure and child trauma (i.e., abuse, neglect, sexual abuse) can have deleterious effects on child development across multiple domains. This study analyzed the impact on childhood neurodevelopment of prenatal alcohol exposure and postnatal traumatic experience compared to postnatal traumatic…

  3. Benzyl alcohol as a marker of occupational exposure to toluene.

    PubMed

    Kawai, Toshio; Yamauchi, Tsuneyuki; Miyama, Yuriko; Sakurai, Haruhiko; Ukai, Hirohiko; Takada, Shiro; Ohashi, Fumiko; Ikeda, Masayuki

    2007-01-01

    Benzyl alcohol (BeOH) is a urinary metabolite of toluene, which has been seldom evaluated for biological monitoring of exposure to this popular solvent. The present study was initiated to develop a practical method for determination of BeOH in urine and to examine if this metabolite can be applied as a marker of occupational exposure to toluene. A practical gas-liquid chromatographic method was successfully developed in the present study with sensitivity low enough for the application (the limit of detection; 5 microg BeOH /l urine with CV=2.7%). Linearity was confirmed up to 10 mg BeOH/l, the highest concentration tested, and the reproducibility was also satisfactory with a coefficient of variation of 2.7% (n=10). A tentative application of the method in a small scale study with 45 male workers [exposed to toluene up to 130 ppm as an 8-h time-weighted average (8-h TWA)] showed that BeOH in the end-of-shift urine samples was proportional to the intensity of exposure to toluene. The calculated regression equation was Y=50+1.7X (r=0.80, p<0.01), where X was toluene in air (in ppm as 8-h TWA) and Y was BeOH in urine (in microg/l of end-of-shift urine). The levels of BeOH in the urine of the non-exposed was about 50 microg/l, and ingestion of benzoate as a preservative in soft drinks did not affect the BeOH level in urine. The findings as a whole suggest that BeOH is a promising candidate for biological monitoring of occupational exposure to toluene.

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

    PubMed

    Blizard, David A; Vandenbergh, David J; Jefferson, Akilah L; Chatlos, Cynthia D; Vogler, George P; McClearn, Gerald E

    2004-01-01

    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

  5. Effects of prenatal alcohol exposure on social behavior in humans and other species.

    PubMed

    Kelly, S J; Day, N; Streissguth, A P

    2000-01-01

    Alcohol exposure during development causes central nervous system alterations in both humans and animals. Although the most common behavioral manifestation of these alterations is a reduction in cognitive abilities, it is becoming increasingly apparent that deficits in social behavior may be very prevalent sequelae of developmental alcohol exposure. In infancy and early childhood, deficits in attachment behavior and state regulation are seen in both alcohol-exposed people and animals, suggesting that these changes are largely the result of the alcohol exposure rather than maternal behavior. In the periadolescent period, people exposed to alcohol during development show a variety of difficulties in the social domain as measured by checklists filled out by either a parent or teacher. Rats exposed to alcohol during development show changes in play and parenting behaviors. In adulthood, prenatal alcohol exposure is related to high rates of trouble with the law, inappropriate sexual behavior, depression, suicide, and failure to care for children. These high rates all suggest that there may be fundamental problems in the social domain. In other animals, perinatal alcohol exposure alters aggression, active social interactions, social communication and recognition, maternal behavior, and sexual behavior in adults. In conclusion, research suggests that people exposed to alcohol during development may exhibit striking changes in social behavior; the animal research suggests that these changes may be largely the result of the alcohol insult and not the environment.

  6. Brief and extended alcohol-cue-exposure effects on craving and attentional bias.

    PubMed

    Ramirez, Jason J; Monti, Peter M; Colwill, Ruth M

    2015-06-01

    Past research has shown that underage college-student drinkers (UCSDs) report increased subjective craving and exhibit stronger attentional biases to alcohol following alcohol-cue exposure. To date, less research has examined whether momentary decreases in alcohol craving are associated with reductions in attentional bias. One experimental manipulation that has been used to produce within-session decreases in alcohol craving is to extend the duration of laboratory-based alcohol-cue exposure protocols. The aim of this study was to examine the effects of both brief and extended alcohol-cue exposure on subjective craving and attentional bias among UCSDs. Eighty participants were randomized either to a group that received a short, in vivo, alcohol-cue-exposure period (short-exposure group [SE], 2 3-min blocks) or to a group that received a long-exposure period (long-exposure group [LE], 6 3-min blocks). Both groups completed a visual probe task before and after cue exposure to assess changes in attentional bias. Analyses revealed no group differences in mean craving or mean attentional bias before or after cue exposure. Further, exploratory analyses revealed no sex differences in our measures of craving or attentional bias. For Group LE, but not Group SE, within-session changes in craving positively predicted within-session changes in attentional bias. However, further analyses revealed that this relationship was significant only for women in the LE group. Implications for treatments that aim to reduce craving and/or attentional bias are discussed.

  7. What Research Is Being Done on Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorders in the Russian Research Community?

    PubMed Central

    Popova, Svetlana; Yaltonskaya, Aleksandra; Yaltonsky, Vladimir; Kolpakov, Yaroslav; Abrosimov, Ilya; Pervakov, Kristina; Tanner, Valeria; Rehm, Jürgen

    2014-01-01

    Aims: Although Russia has one of the highest rates of alcohol consumption and alcohol-attributable burden of disease, little is known about the existing research on prenatal alcohol exposure (PAE) and Fetal Alcohol Spectrum Disorders (FASDs) in this country. The objective of this study was to locate and review published and unpublished studies related to any aspect of PAE and FASD conducted in or using study populations from Russia. Methods: A systematic literature search was conducted in multiple English and Russian electronic bibliographic databases. In addition, a manual search was conducted in several major libraries in Moscow. Results: The search revealed a small pool of existing research studies related to PAE and/or FASD in Russia (126: 22 in English and 104 in Russian). Existing epidemiological data indicate a high prevalence of PAE and FASD, which underlines the strong negative impact that alcohol has on mortality, morbidity and disability in Russia. High levels of alcohol consumption by women of childbearing age, low levels of contraception use, and low levels of knowledge by health and other professionals regarding the harmful effects of PAE put this country at great risk of further alcohol-affected pregnancies. Conclusions: Alcohol preventive measures in Russia warrant immediate attention. More research focused on alcohol prevention and policy is needed in order to reduce alcohol-related harm, especially in the field of FASD. PMID:24158024

  8. Alcohol Increases Liver Progenitor Populations and Induces Disease Phenotypes in Human IPSC-Derived Mature Stage Hepatic Cells

    PubMed Central

    Tian, Lipeng; Deshmukh, Abhijeet; Prasad, Neha; Jang, Yoon-Young

    2016-01-01

    Alcohol consumption has long been a global problem affecting human health, and has been found to influence both fetal and adult liver functions. However, how alcohol affects human liver development and liver progenitor cells remains largely unknown. Here, we used human induced pluripotent stem cells (iPSCs) as a model to examine the effects of alcohol, on multi-stage hepatic cells including hepatic progenitors, early and mature hepatocyte-like cells derived from human iPSCs. While alcohol has little effect on endoderm development from iPSCs, it reduces formation of hepatic progenitor cells during early hepatic specification. The proliferative activities of early and mature hepatocyte-like cells are significantly decreased after alcohol exposure. Importantly, at a mature stage of hepatocyte-like cells, alcohol treatment increases two liver progenitor subsets, causes oxidative mitochondrial injury and results in liver disease phenotypes (i.e., steatosis and hepatocellular carcinoma associated markers) in a dose dependent manner. Some of the phenotypes were significantly improved by antioxidant treatment. This report suggests that fetal alcohol exposure may impair generation of hepatic progenitors at early stage of hepatic specification and decrease proliferation of fetal hepatocytes; meanwhile alcohol injury in post-natal or mature stage human liver may contribute to disease phenotypes. This human iPSC model of alcohol-induced liver injury can be highly valuable for investigating alcoholic injury in the fetus as well as understanding the pathogenesis and ultimately developing effective treatment for alcoholic liver disease in adults. PMID:27570479

  9. Chronic alcohol exposure exacerbates inflammation and triggers pancreatic acinar-to-ductal metaplasia through PI3K/Akt/IKK

    PubMed Central

    HUANG, XIN; LI, XUQI; MA, QINGYONG; XU, QINHONG; DUAN, WANXING; LEI, JIANJUN; ZHANG, LUN; WU, ZHENG

    2015-01-01

    Pancreatic acinar-to-ductal metaplasia (ADM) has been identified as an initiating event that can progress to pancreatic intraepithelial neoplasia (PanIN) or pancreatic ductal adenocarcinoma (PDAC). Acini transdifferentiation can be induced by persistent inflammation. Notably, compelling evidence has emerged that chronic alcohol exposure may trigger an inflammatory response of macrophages/monocytes stimulated by endotoxins. In the present study, we aimed to evaluate the role of inflammation induced by chronic alcohol and lipopolysaccharide (LPS) exposure in the progression of pancreatic ADM, as well as to elucidate the possible mechanisms involved. For this purpose, cultured macrophages were exposed to varying doses of alcohol for 1 week prior to stimulation with LPS. Tumor necrosis factor-α (TNF-α) and regulated upon activation, normal T cell expression and secreted (RANTES) expression were upregulated in the intoxicated macrophages with activated nuclear factor-κB (NF-κB). Following treatment with the supernatant of intoxicated macrophages, ADM of primary acinar cells was induced. Furthermore, the expression of TNF-α and RANTES, as well as the phosphatidylinositol-3-kinase (PI3K)/protein kinase B(Akt)/inhibitory κB kinase (IKK) signaling pathway have been proven to be involved in the ADM of acinar cells. Moreover, Sprague-Dawley (SD) rats were employed to further explore the induction of pancreatic ADM by chronic alcohol and LPS exposure in vivo. At the end of the treatment period, a number of physiological parameters, such as body weight, liver weight and pancreatic weight were reduced in the exposed rats. Plasma alcohol concentrations and oxidative stress levels in the serum, as well as TNF-α and RANTES expression in monocytes were also induced following chronic alcohol and LPS exposure. In addition, pancreatic ADM was induced through the PI3K/Akt/IKK signaling pathway by the augmented TNF-α and RANTES expression levels in the exposed rats. Overall, we

  10. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

    PubMed Central

    Udoh, Uduak S.; Valcin, Jennifer A.; Gamble, Karen L.; Bailey, Shannon M.

    2015-01-01

    Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases. PMID:26473939

  11. Exposure to nicotine during periadolescence or early adulthood alters aversive and physiological effects induced by ethanol.

    PubMed

    Rinker, Jennifer A; Hutchison, Mary Anne; Chen, Scott A; Thorsell, Annika; Heilig, Markus; Riley, Anthony L

    2011-07-01

    The majority of smokers begin their habit during adolescence, which often precedes experimentation with alcohol. Interestingly, very little preclinical work has been done examining how exposure to nicotine during periadolescence impacts the affective properties of alcohol in adulthood. Understanding how periadolescent nicotine exposure influences the aversive effects of alcohol might help to explain why it becomes more acceptable to this preexposed population. Thus, Experiment 1 exposed male Sprague Dawley rats to either saline or nicotine (0.4mg/kg, IP) from postnatal days 34 to 43 (periadolescence) and then examined changes in the aversive effects of alcohol (0, 0.56, 1.0 and 1.8g/kg, IP) in adulthood using the conditioned taste aversion (CTA) design. Changes in blood alcohol concentration (BAC) as well as alcohol-induced hypothermia and locomotor suppression were also assessed. To determine if changes seen were specific to nicotine exposure during periadolescence, the procedures were replicated in adults (Experiment 2). Preexposure to nicotine during periadolescence attenuated the acquisition of the alcohol-induced CTAs (at 1.0g/kg) and the hypothermic effects of alcohol (1.0g/kg). Adult nicotine preexposure produced similar attenuation in alcohol's aversive (at 1.8g/kg) and hypothermic (1.8g/kg) effects. Neither adolescent nor adult nicotine preexposure altered BACs or alcohol-induced locomotor suppression. These results suggest that nicotine may alter the aversive and physiological effects of alcohol, regardless of the age at which exposure occurs, possibly increasing its overall reinforcing value and making it more likely to be consumed.

  12. Catalase prevents elevation of [Ca(2+)](i) induced by alcohol in cultured canine cerebral vascular smooth muscle cells: Possible relationship to alcohol-induced stroke and brain pathology.

    PubMed

    Li, Wenyan; Liu, Weimin; Altura, Bella T; Altura, Burton M

    2003-01-15

    Several studies have suggested that alcohol-induced brain injury is associated with generation of reactive oxygen species (ROS). The recent findings, that antioxidants (Vitamin E and pyrrolidine dithiocarbamate (PDTC)) prevent intracellular Ca(2+) ([Ca(2+)](i)) overload in cerebral vascular smooth muscle cells, induced by alcohol, demonstrate indirectly that ROS formation is related to cerebral vascular injury. The present experiments were designed to test the hypothesis that catalase, an hydrogen peroxide (H(2)O(2)) scavenging enzyme, can prevent or ameliorate alcohol-induced elevation of [Ca(2+)](i). Preincubation of cultured canine cerebral vascular smooth muscle cells with catalase (20-1000 units/ml) didn't produce any apparent changes from controls in resting levels of [Ca(2+)](i) after 1-3 days. Exposure of the cerebral vascular cells to culture media containing 10-100mM ethanol resulted in significant rises in [Ca(2+)](i) (p<0.01). Although exposure of these cells to a low concentration of catalase (20 units/ml) failed to prevent the increased level of [Ca(2+)](i) induced by ethanol, concomitant addition of higher concentrations of catalase (100-1000 units/ml) and ethanol (10-100mM) inhibited or ameliorated the rises of [Ca(2+)](i) induced by ethanol either at 24h or at 3 days, in a concentration-dependent manner. Catalase, in the range of 100-200 units/ml, inhibited approximately 50% of the [Ca(2+)](i) increases caused by ethanol in the first 24h. Catalase at a concentration of 1000 units/ml inhibited completely excessive [Ca(2+)](i) accumulation. The present results when viewed in light of other recently published data suggest that H(2)O(2) generation may be one of the earliest events triggered by alcohol in alcohol-induced brain-vascular damage, neurobehavioral actions and stroke.

  13. Antioxidants prevent depletion of [Mg2+]i induced by alcohol in cultured canine cerebral vascular smooth muscle cells: possible relationship to alcohol-induced stroke.

    PubMed

    Li, W; Zheng, T; Altura, B T; Altura, B M

    2001-07-01

    Low serum concentrations of Mg(2+) ions have been reported, recently, in patients with coronary disease, atherosclerosis, and stroke as well as in patients with cerebral hemorrhage. The aim of the present study was to determine whether potent antioxidants [alpha-tocopherol and pyrrolidine dithiocarbamate (PDTC)] can prevent or ameliorate intracellular Mg(2+) ([Mg(2+)](i)) depletion associated with cerebral vascular injury induced by alcohol. Exposure of cultured canine cerebral vascular smooth muscle cells to alcohol (10-100 mM) for 24 h induced marked depletion in [Mg(2+)](i) (i.e., approximately 30-65%, depending upon alcohol concentration). Treatment of the cultured cells with either PDTC (0.1 microM) or alpha-tocopherol (15 microM) for 24 h, alone, failed to interfere with basal [Mg(2+)](i) levels. However, preincubation of the cells with either alpha-tocopherol or PDTC for 24 h completely inhibited the depletion of [Mg(2+)](i) induced by exposure to 10-100 mM ethanol. These results indicate that alpha-tocopherol and PDTC prevent decreases in [Mg(2+)](i) produced by ethanol. Moreover, these new results suggest that such protective effects of alpha-tocopherol and PDTC on cerebral vascular cells might be useful therapeutic tools in prevention and amelioration of cerebral vascular injury and stroke in alcoholics.

  14. Evaluation of furfuryl alcohol sensitization potential following dermal and pulmonary exposure: enhancement of airway responsiveness.

    PubMed

    Franko, Jennifer; Jackson, Laurel G; Hubbs, Ann; Kashon, Michael; Meade, B J; Anderson, Stacey E

    2012-01-01

    Furfuryl alcohol is considered by the U.S. Environmental Protection Agency to be a high volume production chemical, with over 1 million pounds produced annually. Due to its high production volume and its numerous industrial and consumer uses, there is considerable potential for work-related exposure, as well as exposure to the general population, through pulmonary, oral, and dermal routes of exposure. Human exposure data report a high incidence of asthma in foundry mold workers exposed to furan resins, suggesting potential immunologic effects. Although furfuryl alcohol was nominated and evaluated for its carcinogenic potential by the National Toxicology Program, studies evaluating its immunotoxicity are lacking. The studies presented here evaluated the immunotoxic potential of furfuryl alcohol following exposure by the dermal and pulmonary routes using a murine model. When tested in a combined irritancy local lymph node assay, furfuryl alcohol was identified to be an irritant and mild sensitizer (EC3 = 25.6%). Pulmonary exposure to 2% furfuryl alcohol resulted in enhanced airway hyperreactivity, eosinophilic infiltration into the lungs, and enhanced cytokine production (IL-4, IL-5, and interferon-γ) by ex vivo stimulated lung-associated draining lymphoid cells. Airway hyperreactivity and eosinophilic lung infiltration were augmented by prior dermal exposure to furfuryl alcohol. These results suggest that furfuryl alcohol may play a role in the development of allergic airway disease and encourage the need for additional investigation.

  15. The effects of postnatal alcohol exposure and galantamine on the context pre-exposure facilitation effect and acetylcholine efflux using in vivo microdialysis.

    PubMed

    Perkins, Amy E; Fadel, Jim R; Kelly, Sandra J

    2015-05-01

    Fetal alcohol spectrum disorders (FASD) are characterized by damage to multiple brain regions, including the hippocampus, which is involved in learning and memory. The acetylcholine neurotransmitter system provides major input to the hippocampus and is a possible target of developmental alcohol exposure. Alcohol (3.0 g/kg/day) was administered via intubation to male rat pups (postnatal day [PD] 2-10; ethanol-treated [ET]). Controls received a sham intubation (IC) or no treatment (NC). Acetylcholine efflux was measured using in vivo microdialysis (PD 32-35). ET animals were not different at baseline, but had decreased K(+)/Ca(2+)-induced acetylcholine efflux compared to NC animals and an enhanced acetylcholine response to galantamine (acetylcholinesterase inhibitor; 2.0 mg/kg) compared to both control groups. A separate cohort of animals was tested in the context pre-exposure facilitation effect task (CPFE; PD 30-32) following postnatal alcohol exposure and administration of galantamine (2.0 mg/kg; PD 11-30). Neither chronic galantamine nor postnatal alcohol exposure influenced performance in the CPFE task. Using immunohistochemistry, we found that neither alcohol exposure nor behavioral testing significantly altered the density of vesicular acetylcholine transporter or alpha7 nicotinic acetylcholine receptor in the ventral hippocampus (CA1). In the medial septum, the average number of choline acetyltransferase (ChAT+) cells was increased in ET animals that displayed the context-shock association; there were no changes in IC and NC animals that learned the context-shock association or in any animals that were in the control task that entailed no learning. Taken together, these results indicate that the hippocampal acetylcholine system is significantly disrupted under conditions of pharmacological manipulations (e.g., galantamine) in alcohol-exposed animals. Furthermore, ChAT was up‑regulated in ET animals that learned the CPFE, which may account for their ability

  16. Adolescent binge alcohol exposure alters hippocampal progenitor cell proliferation in rats: effects on cell cycle kinetics.

    PubMed

    McClain, Justin A; Hayes, Dayna M; Morris, Stephanie A; Nixon, Kimberly

    2011-09-01

    Binge alcohol exposure in adolescent rats potently inhibits adult hippocampal neurogenesis by altering neural progenitor cell (NPC) proliferation and survival; however, it is not clear whether alcohol results in an increase or decrease in net proliferation. Thus, the effects of alcohol on hippocampal NPC cell cycle phase distribution and kinetics were assessed in an adolescent rat model of an alcohol use disorder. Cell cycle distribution was measured using a combination of markers (Ki-67, bromodeoxyuridine incorporation, and phosphohistone H3) to determine the proportion of NPCs within G1, S, and G2/M phases of the cell cycle. Cell cycle kinetics were calculated using a cumulative bromodeoxyuridine injection protocol to determine the effect of alcohol on cell cycle length and S-phase duration. Binge alcohol exposure reduced the proportion of NPCs in S-phase, but had no effect on G1 or G2/M phases, indicating that alcohol specifically targets S-phase of the cell cycle. Cell cycle kinetics studies revealed that alcohol reduced NPC cell cycle duration by 36% and shortened S-phase by 62%, suggesting that binge alcohol exposure accelerates progression through the cell cycle. This effect would be expected to increase NPC proliferation, which was supported by a slight, but significant increase in the number of Sox-2+ NPCs residing in the hippocampal subgranular zone following binge alcohol exposure. These studies suggest the mechanism of alcohol inhibition of neurogenesis and also reveal the earliest evidence of the compensatory neurogenesis reaction that has been observed a week after binge alcohol exposure.

  17. A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.

    PubMed

    Marchant, Nathan J; Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M; Bonci, Antonello; Shaham, Yavin

    2014-05-28

    In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse.

  18. Voluntary Alcohol Intake following Blast Exposure in a Rat Model of Mild Traumatic Brain Injury.

    PubMed

    Lim, Yi Wei; Meyer, Nathan P; Shah, Alok S; Budde, Matthew D; Stemper, Brian D; Olsen, Christopher M

    2015-01-01

    Alcoholism is a frequent comorbidity following mild traumatic brain injury (mTBI), even in patients without a previous history of alcohol dependence. Despite this correlational relationship, the extent to which the neurological effects of mTBI contribute to the development of alcoholism is unknown. In this study, we used a rodent blast exposure model to investigate the relationship between mTBI and voluntary alcohol drinking in alcohol naïve rats. We have previously demonstrated in Sprague Dawley rats that blast exposure leads to microstructural abnormalities in the medial prefrontal cortex (mPFC) and other brain regions that progress from four to thirty days. The mPFC is a brain region implicated in alcoholism and drug addiction, although the impact of mTBI on drug reward and addiction using controlled models remains largely unexplored. Alcohol naïve Sprague Dawley rats were subjected to a blast model of mTBI (or sham conditions) and then tested in several common measures of voluntary alcohol intake. In a seven-week intermittent two-bottle choice alcohol drinking test, sham and blast exposed rats had comparable levels of alcohol intake. In a short access test session at the conclusion of the two-bottle test, blast rats fell into a bimodal distribution, and among high intake rats, blast treated animals had significantly elevated intake compared to shams. We found no effect of blast when rats were tested for an alcohol deprivation effect or compulsive drinking in a quinine adulteration test. Throughout the experiment, alcohol drinking was modest in both groups, consistent with other studies using Sprague Dawley rats. In conclusion, blast exposure had a minimal impact on overall alcohol intake in Sprague Dawley rats, although intake was increased in a subpopulation of blast animals in a short access session following intermittent access exposure.

  19. Youth Exposure to Alcohol Use and Brand Appearances in Popular Contemporary Movies

    PubMed Central

    DAL CIN, Sonya; WORTH, Keilah A.; DALTON, Madeline A.; SARGENT, James D.

    2010-01-01

    Aims To describe alcohol use and alcohol brand appearances in popular movies and estimate adolescents’ exposure to this alcohol-related content. Design and setting Nationally representative, random-digit dialed survey in the United States and content analysis of alcohol depictions in the top 100 U.S. box office hits each year from 1998 to 2002 and 34 top movies from early 2003. Participants 6522 U.S. adolescents aged 10-14. Measurements Frequency of alcohol use and brand appearances in movies by Motion Picture Association of America (MPAA) rating. Estimated exposure to minutes of movie alcohol use and brand appearances among U.S. adolescents in this age group. Findings Most movies (83%, including 57% of G/PG-rated movies) depicted alcohol use and 52% (including 19% of G/PG movies) contained at least one alcohol brand appearance, which consisted of branded use by an actor 30% of the time. These movies exposed the average U.S. adolescent 10-14 years of age to 5.6 (95% CI 5.4,5.7) hours of movie alcohol use and 244 (95% CI 238,250) alcohol brand appearances (5 billion in total), mostly from youth-rated movies. Exposure to movie alcohol content was significantly higher among African American youth than youth of other races. Conclusions Alcohol use and brand appearances are frequently portrayed in popular U.S. movies (which are distributed worldwide). Children and adolescents in the U.S. are exposed to hours of alcohol use depictions and numerous brand appearances in movies and most of this exposure is from movies rated for this segment of the population. PMID:18705684

  20. Cold-inducible RNA-binding protein is an important mediator of alcohol-induced brain inflammation.

    PubMed

    Rajayer, Salil R; Jacob, Asha; Yang, Weng-Lang; Zhou, Mian; Chaung, Wayne; Wang, Ping

    2013-01-01

    Binge drinking has been associated with cerebral dysfunction. Ethanol induced microglial activation initiates an inflammatory process that causes upregulation of proinflammatory cytokines which in turn creates neuronal inflammation and damage. However, the molecular mechanism is not fully understood. We postulate that cold-inducible RNA-binding protein (CIRP), a novel proinflammatory molecule, can contribute to alcohol-induced neuroinflammation. To test this theory male wild-type (WT) mice were exposed to alcohol at concentrations consistent to binge drinking and blood and brain tissues were collected. At 5 h after alcohol, a significant increase of 53% in the brain of CIRP mRNA was observed and its expression remained elevated at 10 h and 15 h. Brain CIRP protein levels were increased by 184% at 10 h and remained high at 15 h. We then exposed male WT and CIRP knockout (CIRP(-/-)) mice to alcohol, and blood and brain tissues were collected at 15 h post-alcohol infusion. Serum levels of tissue injury markers (AST, ALT and LDH) were significantly elevated in alcohol-exposed WT mice while they were less increased in the CIRP(-/-) mice. Brain TNF-α mRNA and protein expressions along with IL-1β protein levels were significantly increased in WT mice, which was not seen in the CIRP(-/-) mice. In cultured BV2 cells (mouse microglia), ethanol at 100 mM showed an increase of CIRP mRNA by 274% and 408% at 24 h and 48 h respectively. Corresponding increases in TNF-α and IL-1β were also observed. CIRP protein levels were markedly increased in the medium, suggesting that CIRP was secreted by the BV2 cells. From this we conclude that alcohol exposure activates microglia to produce and secrete CIRP and possibly induce pro-inflammatory response and thereby causing neuroinflammation. CIRP could be a novel mediator of alcohol-induced brain inflammation.

  1. Thymoquinone Inhibition of Acquisition and Expression of Alcohol-Induced Behavioral Sensitization.

    PubMed

    Khan, Muhammad Sona; Gohar, Aneela; Abbas, Ghulam; Mahmood, Wajahat; Rauf, Khalid; Sewell, Robert D E

    2015-10-01

    Repeated low doses of alcohol have been shown to progressively enhance locomotor activity in mice, and this phenomenon is designated as behavioral sensitization. Thymoquinone, a major active component of Nigella sativa oil has been investigated in a number of studies for its neuroprotective effects against a variety of ailments. This study was conducted to explore the therapeutic potential of thymoquinone on the acquisition and expression of alcohol-induced behavioral sensitization. Mice treated with alcohol (2.2 g/kg/day) or saline for 13 days and subsequently challenged with an acute alcohol dose (2.2 g/kg) 5 days later were orally administered acute doses of thymoquinone (10, 20 and 30 mg/kg). Thymoquinone subacute treatment with all doses throughout alcohol exposure significantly inhibited both the development and expression phases of alcohol behavioral sensitization in a dose-dependent manner. However, acute treatment with thymoquinone (30 mg/kg) only reversed the expression phase of sensitization. These findings are explained in terms of the known GABA promoting action of thymoquinone in relation to the motive circuit within the limbic component of the basal ganglia. It is concluded that thymoquinone may be a potential therapeutic option for the treatment and prevention of alcohol induced behavioral sensitization.

  2. Children’s Exposure to Parental Conflict after Father’s Treatment for Alcoholism

    PubMed Central

    Rounsaville, Daniel; O’Farrell, Timothy J.; Andreas, Jasmina Burdzovic; Murphy, Christopher M.; Murphy, Marie M.

    2014-01-01

    Objective This study investigated children of alcoholics’ (COAs’) exposure to inter-parental conflict before and after their fathers received alcohol treatment and compared exposure levels to a community comparison sample. Method This study included 67 couples with a treatment-seeking male alcoholic partner and children aged 4–16. The alcoholic fathers and their relationship partners provided data at baseline and at six and twelve months follow-up. A community comparison sample of 78 couples with children in the target age range completed similar longitudinal assessments. It was hypothesized that treatment of paternal alcoholism would be associated with a decrease in COAs’ exposure to conflict, and that among remitted patients exposure to conflict would decrease to the level found in the community sample. Results Prior to the father’s alcohol treatment, the children of the treatment sample were exposed to significantly more conflict between their parents than in the community comparison sample. After the fathers received alcohol treatment, COAs’ exposure to conflict significantly decreased at both the six and twelve month follow-ups compared to baseline. Children of remitted alcoholics did not differ significantly in levels of exposure to conflict at six months follow-up compared with the community sample as predicted. However, at twelve months remitted alcoholics reported significantly more exposure to conflict compared to the community sample. Conclusions Decreased child exposure to parental conflict is a benefit associated with the father’s treatment for alcoholism, and it may lead to improvements in COAs’ functioning after parental treatment. PMID:24727114

  3. Youth exposure to alcohol advertising on radio--United States, June-August 2004.

    PubMed

    2006-09-01

    In the United States, more underage youth drink alcohol than smoke tobacco or use illicit drugs. Excessive alcohol consumption leads to many adverse health and social consequences and results in approximately 4,500 deaths among underage youth each year. Recent studies have emphasized the contribution of alcohol marketing to underage drinking and have demonstrated that a substantial proportion of alcohol advertising appears in media for which the audience composition is youth-oriented (i.e., composed disproportionately of persons aged 12-20 years). To determine the proportion of radio advertisements that occurred on radio programs with audiences composed disproportionately of underage youth and the proportion of total youth exposure to alcohol advertising that occurs as a result of such advertising, researchers at the Center on Alcohol Marketing and Youth (Health Policy Institute, Georgetown University, District of Columbia) evaluated the placement of individual radio advertisements for the most advertised U.S. alcohol brands and the composition of audiences in the largest 104 markets in the United States. This report summarizes the results of that study, which indicate that alcohol advertising is common on radio programs which have disproportionately large youth audiences and that this advertising accounts for a substantial proportion of all alcohol radio advertising heard by underage youth. These results further indicate that 1) the current voluntary standards limiting alcohol marketing to youth should be enforced and ultimately strengthened, and 2) ongoing monitoring of youth exposure to alcohol advertising should continue.

  4. Alcohol enhancement of marihuana-induced fetotoxicity.

    PubMed

    Abel, E L

    1985-02-01

    In two separate studies marihuana and alcohol were administered, either separately or in combination, to pregnant mice or rats. Control animals were given vehicle only or were nontreated. Marihuana-, alcohol-, and vehicle-treated animals were pair-fed and pair watered with animals given marihuana plus alcohol, to control for drug-related undernutrition. The combination of marihuana and alcohol caused a 100% fetomortality in mice and a 73% fetomortality in rats, whereas neither marihuana nor alcohol alone had any effects on fetomortality that differed significantly from vehicle treatment. These studies suggest a potential danger to pregnancy resulting from the combined use of two commonly used drugs that is far greater than that associated with use of either drug alone.

  5. Alcohol-Induced Molecular Dysregulation in Human Embryonic Stem Cell-Derived Neural Precursor Cells.

    PubMed

    Kim, Yi Young; Roubal, Ivan; Lee, Youn Soo; Kim, Jin Seok; Hoang, Michael; Mathiyakom, Nathan; Kim, Yong

    Adverse effect of alcohol on neural function has been well documented. Especially, the teratogenic effect of alcohol on neurodevelopment during embryogenesis has been demonstrated in various models, which could be a pathologic basis for fetal alcohol spectrum disorders (FASDs). While the developmental defects from alcohol abuse during gestation have been described, the specific mechanisms by which alcohol mediates these injuries have yet to be determined. Recent studies have shown that alcohol has significant effect on molecular and cellular regulatory mechanisms in embryonic stem cell (ESC) differentiation including genes involved in neural development. To test our hypothesis that alcohol induces molecular alterations during neural differentiation we have derived neural precursor cells from pluripotent human ESCs in the presence or absence of ethanol treatment. Genome-wide transcriptomic profiling identified molecular alterations induced by ethanol exposure during neural differentiation of hESCs into neural rosettes and neural precursor cell populations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis on significantly altered genes showed potential ethanol's effect on JAK-STAT signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, cytokine-cytokine receptor interaction and regulation of autophagy. We have further quantitatively verified ethanol-induced alterations of selected candidate genes. Among verified genes we further examined the expression of P2RX3, which is associated with nociception, a peripheral pain response. We found ethanol significantly reduced the level of P2RX3 in undifferentiated hESCs, but induced the level of P2RX3 mRNA and protein in hESC-derived NPCs. Our result suggests ethanol-induced dysregulation of P2RX3 along with alterations in molecules involved in neural activity such as neuroactive ligand-receptor interaction may be a molecular event

  6. Alcohol-Induced Molecular Dysregulation in Human Embryonic Stem Cell-Derived Neural Precursor Cells

    PubMed Central

    Kim, Yi Young; Roubal, Ivan; Lee, Youn Soo; Kim, Jin Seok; Hoang, Michael; Mathiyakom, Nathan; Kim, Yong

    2016-01-01

    Adverse effect of alcohol on neural function has been well documented. Especially, the teratogenic effect of alcohol on neurodevelopment during embryogenesis has been demonstrated in various models, which could be a pathologic basis for fetal alcohol spectrum disorders (FASDs). While the developmental defects from alcohol abuse during gestation have been described, the specific mechanisms by which alcohol mediates these injuries have yet to be determined. Recent studies have shown that alcohol has significant effect on molecular and cellular regulatory mechanisms in embryonic stem cell (ESC) differentiation including genes involved in neural development. To test our hypothesis that alcohol induces molecular alterations during neural differentiation we have derived neural precursor cells from pluripotent human ESCs in the presence or absence of ethanol treatment. Genome-wide transcriptomic profiling identified molecular alterations induced by ethanol exposure during neural differentiation of hESCs into neural rosettes and neural precursor cell populations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis on significantly altered genes showed potential ethanol’s effect on JAK-STAT signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, cytokine-cytokine receptor interaction and regulation of autophagy. We have further quantitatively verified ethanol-induced alterations of selected candidate genes. Among verified genes we further examined the expression of P2RX3, which is associated with nociception, a peripheral pain response. We found ethanol significantly reduced the level of P2RX3 in undifferentiated hESCs, but induced the level of P2RX3 mRNA and protein in hESC-derived NPCs. Our result suggests ethanol-induced dysregulation of P2RX3 along with alterations in molecules involved in neural activity such as neuroactive ligand-receptor interaction may be a molecular event

  7. Trait modulation of alcohol-induced laboratory aggression.

    PubMed

    Bailly, Matthew D; King, Alan R

    2006-06-15

    Modest alcohol and aggressive trait effects on laboratory-induced aggression among men have been reported with some consistency in the literature. Relationships between aggressive personality traits and laboratory-induced aggression appear to become less consistent under the influence of alcohol. Several research teams have found suggestions that the effects of alcohol on laboratory aggression may be reduced or even reversed among individuals with aggressive personality traits. This study examined the effects of alcohol on the aggressive responding on the Point Subtraction Aggression Paradigm (PSAP) of eight undergraduate men who generated evidence on the Million Clinical Multiaxial Inventory-II (MCMI-II) of sadistic-aggressive personality disorder features. This sample was compared with a group of 18 undergraduate male peers without MCMI-II elevations described in a previous study. Neither alcohol ingestion (0.8 ml/kg) nor aggressive personality traits predicted laboratory behavior in isolation, but alcohol was found to selectively attenuate (d = 0.75) PSAP responding for the sadistic-aggressive as opposed to the control subjects (i.e., a significant aggressive trait by alcohol interaction). The possible value of this counterintuitive response tendency in identifying men at elevated risk for alcohol-related aggression was discussed. Large, immediate reductions in laboratory-based aggressive responding while under the influence of alcohol might provide a paradoxical high risk indicator that has not been previously identified.

  8. Chronic alcohol exposure differentially affects activation of female locus coeruleus neurons and the subcellular distribution of corticotropin releasing factor receptors.

    PubMed

    Retson, T A; Reyes, B A; Van Bockstaele, E J

    2015-01-02

    Understanding the neurobiological bases for sex differences in alcohol dependence is needed to help guide the development of individualized therapies for alcohol abuse disorders. In the present study, alcohol-induced adaptations in (1) anxiety-like behavior, (2) patterns of c-Fos activation and (3) subcellular distribution of corticotropin releasing factor receptor in locus coeruleus (LC) neurons was investigated in male and female Sprague-Dawley rats that were chronically exposed to ethanol using a liquid diet. Results confirm and extend reports by others showing that chronic ethanol exposure produces an anxiogenic-like response in both male and female subjects. Ethanol-induced sex differences were observed with increased c-Fos expression in LC neurons of female ethanol-treated subjects compared to controls or male subjects. Results also reveal sex differences in the subcellular distribution of the CRFr in LC-noradrenergic neurons with female subjects exposed to ethanol exhibiting a higher frequency of plasmalemmal CRFrs. These adaptations have implications for LC neuronal activity and its neural targets across the sexes. Considering the important role of the LC in ethanol-induced activation of the hypothalamo-pituitary-adrenal (HPA) axis, the present results indicate important sex differences in feed-forward regulation of the HPA axis that may render alcohol dependent females more vulnerable to subsequent stress exposure.

  9. Measuring youth exposure to alcohol marketing on social networking sites: challenges and prospects.

    PubMed

    Jernigan, David H; Rushman, Anne E

    2014-02-01

    Youth exposure to alcohol marketing has been linked to increased alcohol consumption and problems. On relatively new and highly interactive social networking sites (SNS) that are popular with youth, tools for measuring youth exposure to alcohol marketing in traditional media are inadequate. We critically review the existing policies of Facebook, Twitter, and YouTube designed to keep branded alcohol content away from underage youth. Looking at brand and user activity on Facebook for the 15 alcohol brands most popular among US youth, we found activity has grown dramatically in the past 3 years, and underage users may be accounting for some of this activity. Surveys of youth and adult participation in alcohol marketing on SNS will be needed to inform debate over these marketing practices.

  10. Fetal alcohol spectrum disorders-- implications for child neurology, part 1: prenatal exposure and dosimetry.

    PubMed

    Paintner, Ashley; Williams, Andrew D; Burd, Larry

    2012-02-01

    In the United States, approximately 80 000 women consume ethanol through all 3 trimesters of pregnancy each year. In this article, we review prevalence rates of prenatal alcohol exposure in the United States and discuss the mechanisms of prenatal alcohol exposure and placental-umbilical effects. Cigarette smoking and delayed prenatal care are often associated with prenatal alcohol exposure. In addition, increased risk for postnatal adversity is common, including maternal depression, foster care placement, and developmental delay. In part 2, we review prevalence rates and the diagnostic criteria for fetal alcohol spectrum disorder and the implications for child neurologists. We discuss management strategies and the importance of a long-term management plan and anticipatory management to prevent the development of secondary disabilities in fetal alcohol spectrum disorders. Child neurologists play a key role in diagnosis and the development of appropriate intervention programs for affected children and their families.

  11. The Activation Effects of Low Level Isopropyl Alcohol Exposure on Arterial Blood Pressures Are Associated with Decreased 5-Hydroxyindole Acetic Acid in Urine

    PubMed Central

    Zhao, Zhiqiang; Liu, Xinxia; Xing, Xiumei; Lu, Yao; Sun, Yi; Ou, Xiaoyan; Su, Xiaolin; Jiang, Jun; Yang, Yarui; Chen, Jingli; Shen, Biling; He, Yun

    2016-01-01

    Purposes The objectives of this paper are to study the impact of low level isopropyl alcohol exposure on blood pressure and to explore its potential mechanism. Methods This cross-sectional study was based on a prospective occupational cohort in south China, which focusing on occupational risk factors related cardiovascular health problems. A total of 283 participants (200 low isopropyl alcohol exposed workers and 83 controls) was finally enrolled in this study. Linear regression models were used to analyze the relationship between arterial blood pressures and low level isopropyl alcohol exposure. We used mediation method to explore possible mediated roles of neurogenic factors. Results Systolic blood pressure (SBP, 123±10 vs. 118±11), diastolic blood pressure (DBP, 79±7 vs. 74±7) and mean blood pressure (MBP, 93±8 vs. 89±9) were different between the exposed group and the control group (p < 0.01). After adjusting for covariates, the difference was still significant. Besides, isopropyl alcohol and smoking had an interactive effect on DBP and MBP (p < 0.05). Furthermore, we observed a mediated effect of 5-hydroxyindole acetic acid (5-HIAA) on isopropyl alcohol exposure induced arterial blood pressure increase, which accounted for about 25%. Conclusions Our results suggest that low level isopropyl alcohol exposure is a potential risk factor for the increased arterial blood pressure and 5-HIAA partly mediates the association between low level isopropyl alcohol exposure and arterial blood pressures. PMID:27622502

  12. An examination of sex differences in the effects of early-life opiate and alcohol exposure.

    PubMed

    Terasaki, Laurne S; Gomez, Julie; Schwarz, Jaclyn M

    2016-02-19

    Early-life exposure to drugs and alcohol is one of the most preventable causes of developmental, behavioural and learning disorders in children. Thus a significant amount of basic, animal and human research has focused on understanding the behavioural consequences and the associated neural effects of exposure to drugs and alcohol during early brain development. Despite this, much of the previous research that has been done on this topic has used predominantly male subjects or rodents. While many of the findings from these male-specific studies may ultimately apply to females, the purpose of this review is to highlight the research that has also examined sex as a factor and found striking differences between the sexes in their response to early-life opiate and alcohol exposure. Finally, we will also provide a framework for scientists interested in examining sex as a factor in future experiments that specifically examine the consequences of early-life drug and alcohol exposure.

  13. An examination of sex differences in the effects of early-life opiate and alcohol exposure

    PubMed Central

    Terasaki, Laurne S.; Gomez, Julie; Schwarz, Jaclyn M.

    2016-01-01

    Early-life exposure to drugs and alcohol is one of the most preventable causes of developmental, behavioural and learning disorders in children. Thus a significant amount of basic, animal and human research has focused on understanding the behavioural consequences and the associated neural effects of exposure to drugs and alcohol during early brain development. Despite this, much of the previous research that has been done on this topic has used predominantly male subjects or rodents. While many of the findings from these male-specific studies may ultimately apply to females, the purpose of this review is to highlight the research that has also examined sex as a factor and found striking differences between the sexes in their response to early-life opiate and alcohol exposure. Finally, we will also provide a framework for scientists interested in examining sex as a factor in future experiments that specifically examine the consequences of early-life drug and alcohol exposure. PMID:26833841

  14. Epilogue: Understanding Children Who Have Been Affected by Maltreatment and Prenatal Alcohol Exposure--Future Directions

    ERIC Educational Resources Information Center

    Hyter, Yvette D.; Way, Ineke

    2007-01-01

    This epilogue summarizes the six articles presented in the clinical forum focused on understanding children who have been affected by maltreatment and prenatal alcohol exposure. It presents common themes that emerged among the articles and future research directions.

  15. Media Exposure and Tobacco, Illicit Drugs, and Alcohol Use among Children and Adolescents: A Systematic Review

    ERIC Educational Resources Information Center

    Nunez-Smith, Marcella; Wolf, Elizabeth; Huang, Helen Mikiko; Chen, Peggy G.; Lee, Lana; Emanuel, Ezekiel J.; Gross, Cary P.

    2010-01-01

    The authors systematically reviewed 42 quantitative studies on the relationship between media exposure and tobacco, illicit drug, and alcohol use among children and adolescents. Overall, 83% of studies reported that media was associated with increased risk of smoking initiation, use of illicit drugs, and alcohol consumption. Of 30 studies…

  16. Prenatal Alcohol and Cocaine Exposure: Influences on Cognition, Speech, Language, and Hearing

    ERIC Educational Resources Information Center

    Cone-Wesson, B.

    2005-01-01

    This paper reviews research on the consequences of prenatal exposure to alcohol and cocaine on children's speech, language, hearing, and cognitive development. The review shows that cognitive impairment, learning disabilities, and behavioral disorders are the central nervous system manifestations of fetal alcohol syndrome (FAS), and cranio-facial…

  17. Oats supplementation prevents alcohol-induced gut leakiness in rats by preventing alcohol-induced oxidative tissue damage.

    PubMed

    Tang, Yueming; Forsyth, Christopher B; Banan, Ali; Fields, Jeremy Z; Keshavarzian, Ali

    2009-06-01

    We reported previously that oats supplementation prevents gut leakiness and alcoholic steatohepatitis (ASH) in our rat model of alcoholic liver disease. Because oxidative stress is implicated in the pathogenesis of both alcohol-induced gut leakiness and ASH, and because oats have antioxidant properties, we tested the hypothesis that oats protect by preventing alcohol-induced oxidative damage to the intestine. Male Sprague-Dawley rats were gavaged for 12 weeks with alcohol (starting dose of 1 g/kg increasing to 6 g/kg/day over the first 2 weeks) or dextrose, with or without oats supplementation (10 g/kg/day). Oxidative stress and injury were assessed by measuring colonic mucosal inducible nitric-oxide synthase (iNOS) (by immunohistochemistry), nitric oxide (colorimetric assay), and protein carbonylation and nitrotyrosination (immunoblotting). Colonic barrier integrity was determined by assessing the integrity of the actin cytoskeleton (immunohistochemistry) and the integrity of tight junctions (electron microscopy). Oats supplementation prevented alcohol-induced up-regulation of iNOS, nitric oxide overproduction in the colonic mucosa, and increases in protein carbonyl and nitrotyrosine levels. This protection was associated with prevention of ethanol (EtOH)-induced disorganization of the actin cytoskeleton and disruption of tight junctions. We conclude that oats supplementation attenuates EtOH-induced disruption of intestinal barrier integrity, at least in part, by inhibiting EtOH-induced increases in oxidative stress and oxidative tissue damage. This inhibition prevents alcohol-induced disruption of the cytoskeleton and tight junctions. This study suggests that oats may be a useful therapeutic agent--a nutraceutical--for the prevention of alcohol-induced oxidative stress and organ dysfunction.

  18. Fetal Alcohol Spectrum Disorders: Understanding the Effects of Prenatal Alcohol Exposure and Supporting Students

    ERIC Educational Resources Information Center

    Green, Jennifer H.

    2007-01-01

    Background: Fetal Alcohol Spectrum Disorders (FASD) affect a significant number of children in this country. This article addresses diagnostic issues related to fetal alcohol syndrome (FAS) and other alcohol-related disabilities, discusses associated features and behaviors of FASD, and introduces interventions to support children with FASD in…

  19. The incidence of prenatal alcohol exposure in Montevideo Uruguay as determined by meconium analysis.

    PubMed

    Hutson, Janine R; Magri, Raquel; Gareri, Joey N; Koren, Gideon

    2010-06-01

    Prenatal alcohol exposure can lead to a wide range of deficits known as fetal alcohol spectrum disorder. Epidemiologic studies regarding alcohol consumption in pregnancy have concentrated on North America, but recent reports have suggested that consumption is significant in many parts of the world. In Uruguay, alcohol consumption has changed into more risky and dangerous patterns and thus has a theoretical risk of having a high rate of prenatal alcohol exposure. This study characterizes the incidence of prenatal alcohol exposure in Montevideo, Uruguay, using a novel biomarker, fatty acid ethyl esters, in meconium as well as a survey to mothers. Nine hundred five meconium samples were collected from Hospital Pereira Rossell and Hospital de Clínicas in Montevideo, Uruguay. A maternal questionnaire was also completed. Meconium was analyzed for fatty acid ethyl esters using liquid-liquid and solid phase extraction with gas chromatography-flame ionization detection. Meconium was also analyzed for other drugs of abuse using enzyme-linked immunosorbent assay. Forty-four percent of meconium samples were above the positive cutoff for fatty acid ethyl esters and represent those newborns with risky prenatal exposure during the final two trimesters of pregnancy. Infants with prenatal alcohol exposure were more likely to have prenatal exposure to tobacco (odds ratio, 1.56; 95% confidence interval, 1.11-2.20) or any illicit drug (odds ratio, 2.29; 95% confidence interval, 0.98-5.31). Ethyl linoleate was a significant predictor of infant birth weight along with prenatal tobacco exposure, maternal body mass index, and infant sex. This study highlights a 44% incidence of prenatal alcohol exposure.

  20. Exposure of African-American Youth to Alcohol Advertising.

    ERIC Educational Resources Information Center

    2003

    The marketing of alcohol products in African-American communities has, on occasion, stirred national controversy and met with fierce resistance from African Americans and others. Despite occasional media and community spotlights on the marketing of alcohol products in the African-American community, there has been no systematic review of the…

  1. Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure

    PubMed Central

    Treit, Sarah; Zhou, Dongming; Chudley, Albert E.; Andrew, Gail; Rasmussen, Carmen; Nikkel, Sarah M.; Samdup, Dawa; Hanlon-Dearman, Ana; Loock, Christine; Beaulieu, Christian

    2016-01-01

    Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5–19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol

  2. Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure.

    PubMed

    Treit, Sarah; Zhou, Dongming; Chudley, Albert E; Andrew, Gail; Rasmussen, Carmen; Nikkel, Sarah M; Samdup, Dawa; Hanlon-Dearman, Ana; Loock, Christine; Beaulieu, Christian

    2016-01-01

    Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5-19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol

  3. Associations of alcohol use with mental health and alcohol exposure among school-going students in Cambodia

    PubMed Central

    Peltzer, Karl; Pengpid, Supa; Tepirou, Chher

    2016-01-01

    ABSTRACT The aim of this study was to examine the associations of alcohol use with sociodemographic factors, mental health and alcohol exposure among school-going adolescents in Cambodia. The analysis included 3,806 school children, mean age 15.7 years (SD=1.8), from Cambodia who participated in the “Global School-based Student Health Survey” (GSHS) in 2013. The results indicate that overall, 10.0% of the students reported current alcohol use, 10.8% lifetime drunkenness, and 2.8% problem drinking. In multivariate logistic regression analysis, sociodemographic factors (older age and being male), mental health and other variables (bullying victimization, OR (odds ratio) = 1.99; 95% Confidence Interval (CI) [1.50, 2.65] and OR = 2.15; 95% CI [1.58, 3.21], respectively; having attempted suicide, OR = 2.04; 95% CI [1.35, 3.08] and OR = 2.06; 95% CI [1.29, 3.28], respectively and illicit drug use, OR = 4.97; 95% CI [2.41, 10.24] OR = 5.05; 95% CI [2.14, 11.98], respectively) and alcohol exposure variables (peer influence on drinking alcohol, OR = 6.68; 95% CI [4.75, 9.39] and OR = 7.83; 95% CI [5.73, 10.66], respectively and daily or almost daily to alcohol advertising in the past 30 days OR = 1.61; 95% CI [1.03, 2.51] and OR = 2.30; 95% CI [1.40, 3.77], respectively) were significantly positively associated with current alcohol use and drunkenness. Moreover, older age, being male, bullying victimization, having close friends, suicide attempt, drug use, father or male guardian drinks alcohol and peer influence were associated with problem drinking. There is a need to implement public health interventions with a special focus on the determinants of alcohol consumption, including exposure to alcohol advertising, in this age group. PMID:28008197

  4. Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

    PubMed

    Bahi, Amine

    2013-07-01

    Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

  5. Vasopressin Regulation and Renal Fluid and Electrolyte Handling in Rat Models of Acute and Chronic alcohol Exposure

    DTIC Science & Technology

    2004-10-01

    evaluating fluid and electrolyte regulating ability in models of acute and chronic alcohol exposure and alcohol withdrawal, and 2) uncovering mechanisms ...be used to define mechanisms behind alcohol effects better than study of humans because conditions of alcohol dosing, hydration status, and fluid...vasopressin receptor regulation, and have determined that altered renal responsiveness to vasopressin is the main mechanism behind fluid balance perturbations

  6. Hypothalamic-pituitary-adrenal axis and behavioral dysfunction following early binge-like prenatal alcohol exposure in mice.

    PubMed

    Wieczorek, Lindsay; Fish, Eric W; O'Leary-Moore, Shonagh K; Parnell, Scott E; Sulik, Kathleen K

    2015-05-01

    The range of defects that fall within fetal alcohol spectrum disorder (FASD) includes persistent behavioral problems, with anxiety and depression being two of the more commonly reported issues. Previous studies of rodent FASD models suggest that interference with hypothalamic-pituitary-adrenal (HPA) axis structure and/or function may be the basis for some of the prenatal alcohol (ethanol) exposure (PAE)-induced behavioral abnormalities. Included among the previous investigations are those illustrating that maternal alcohol treatment limited to very early stages of pregnancy (i.e., gestational day [GD]7 in mice; equivalent to the third week post-fertilization in humans) can cause structural abnormalities in areas such as the hypothalamus, pituitary gland, and other forebrain regions integral to controlling stress and behavioral responses. The current investigation was designed to further examine the sequelae of prenatal alcohol insult at this early time period, with particular attention to HPA axis-associated functional changes in adult mice. The results of this study reveal that GD7 PAE in mice causes HPA axis dysfunction, with males and females showing elevated corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, respectively, following a 15-min restraint stress exposure. Males also showed elevated CORT levels following an acute alcohol injection of 2.0 g/kg, while females displayed blunted ACTH levels. Furthermore, analysis showed that anxiety-like behavior was decreased after GD7 PAE in female mice, but was increased in male mice. Collectively, the results of this study show that early gestational alcohol exposure in mice alters long-term HPA axis activity and behavior in a sexually dimorphic manner.

  7. Hypothalamic-pituitary-adrenal axis and behavioral dysfunction following early binge-like prenatal alcohol exposure in mice

    PubMed Central

    Wieczorek, Lindsay; Fish, Eric W.; O’Leary-Moore, Shonagh K.; Parnell, Scott E.; Sulik, Kathleen K.

    2015-01-01

    The range of defects that fall within fetal alcohol spectrum disorder (FASD) includes persistent behavioral problems, with anxiety and depression being two of the more commonly reported issues. Previous studies of rodent FASD models suggest that interference with hypothalamic-pituitary-adrenal (HPA) axis structure and/or function may be the basis for some of the prenatal alcohol (ethanol) exposure (PAE)-induced behavioral abnormalities. Included among the previous investigations are those illustrating that maternal alcohol treatment limited to very early stages of pregnancy (i.e., gestational day [GD]7 in mice; equivalent to the third week post-fertilization in humans) can cause structural abnormalities in areas such as the hypothalamus, pituitary gland, and other forebrain regions integral to controlling stress and behavioral responses. The current investigation was designed to further examine the sequelae of prenatal alcohol insult at this early time period, with particular attention to HPA axis-associated functional changes in adult mice. The results of this study reveal that GD7 PAE in mice causes HPA axis dysfunction, with males and females showing elevated corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, respectively, following a 15-min restraint stress exposure. Males also showed elevated CORT levels following an acute alcohol injection of 2.0 g/kg, while females displayed blunted ACTH levels. Furthermore, analysis showed that anxiety-like behavior was decreased after GD7 PAE in female mice, but was increased in male mice. Collectively, the results of this study show that early gestational alcohol exposure in mice alters long-term HPA axis activity and behavior in a sexually dimorphic manner. PMID:25709101

  8. Hippocampal neuron populations are reduced in vervet monkeys with fetal alcohol exposure.

    PubMed

    Burke, Mark W; Ptito, Maurice; Ervin, Frank R; Palmour, Roberta M

    2015-05-01

    Prenatal exposure to beverage alcohol is a major cause of mild mental retardation and developmental delay. In nonendangered alcohol-preferring vervet monkeys, we modeled the most common nondysmorphic form of fetal alcohol syndrome disorder with voluntary drinking during the third trimester of pregnancy. Here, we report significant numerical reductions in the principal hippocampal neurons of fetal alcohol-exposed (FAE) offspring, as compared to age-matched, similarly housed conspecifics with isocaloric sucrose exposure. These deficits, particularly marked in CA1 and CA3, are present neonatally and persist through infancy (5 months) and juvenile (2 years) stages. Although the volumes of hippocampal subdivisions in FAE animals are not atypical at birth, by age 2, they are only 65-70% of those estimated in age-matched controls. These data suggest that moderate, naturalistic alcohol consumption during late pregnancy results in a stable loss of hippocampal neurons and a progressive reduction of hippocampal volume.

  9. New Treatment Strategies for Alcohol-Induced Heart Damage

    PubMed Central

    Fernández-Solà, Joaquim; Planavila Porta, Ana

    2016-01-01

    High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis. In addition, ethanol decreases myocyte protective and repair mechanisms and their regeneration. Although there are diverse different strategies to directly target alcohol-induced heart damage, they are partially effective, and can only be used as support medication in a multidisciplinary approach. Alcohol abstinence is the preferred goal, but control drinking is useful in alcohol-addicted subjects not able to abstain. Correction of nutrition, ionic and vitamin deficiencies and control of alcohol-related systemic organ damage are compulsory. Recently, several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCK inhibitors) and new cardiomyokines such as FGF21 have been described to regulate cardiac plasticity and decrease cardiac damage, improving cardiac repair mechanisms, and they are promising agents in this field. New potential therapeutic targets aim to control oxidative damage, myocyte hypertrophy, interstitial fibrosis and persistent apoptosis In addition, stem-cell therapy may improve myocyte regeneration. However, these strategies are not yet approved for clinical use. PMID:27690014

  10. Impaired odor identification in children with histories of heavy prenatal alcohol exposure.

    PubMed

    Bower, Emily; Szajer, Jacquelyn; Mattson, Sarah N; Riley, Edward P; Murphy, Claire

    2013-06-01

    Prenatal alcohol exposure can lead to behavioral and cognitive impairments across multiple domains. Many of the brain regions impacted by prenatal alcohol exposure are also linked with olfactory processing, and odor identification deficits have been documented in certain neurological disorders associated with these brain regions. As odor identification following prenatal alcohol exposure is not well studied, we compared odor identification in children with prenatal exposure to alcohol (AE) to typically developing controls (CON) (N = 16/group). It was hypothesized that children in the AE group would perform more poorly than children in the CON group on the San Diego Odor Identification Test, an identification test of 8 common household odorants. Children exposed to alcohol during prenatal development were significantly impaired in olfactory identification (M = 5.95, SE = 0.37) compared to typically developing controls (M = 7.24, SE = 0.37). These findings confirmed the hypothesis that prenatal exposure to alcohol is associated with odor identification deficits, and suggest that further research is warranted to identify the mechanisms underlying these deficits, the integrity of brain areas that are involved, and to determine whether olfactory performance might contribute to better identification of children at risk for behavioral and cognitive deficits.

  11. Acute and chronic ethanol exposure differentially alters alcohol dehydrogenase and aldehyde dehydrogenase activity in the zebrafish liver.

    PubMed

    Tran, Steven; Nowicki, Magda; Chatterjee, Diptendu; Gerlai, Robert

    2015-01-02

    Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantly reduced locomotor response and increased ADH activity, however, ALDH activity did not change. Zebrafish that were repeatedly exposed to ethanol demonstrated a small but significant attenuation of the locomotor response during the acute ethanol challenge but ADH and ALDH activity was similar to controls. Overall, we identified two different chronic ethanol exposure paradigms that differentially alter behavioral and physiological responses in zebrafish. We speculate that these two paradigms may allow dissociation of central nervous system-related and liver enzyme-dependent ethanol induced changes in zebrafish.

  12. Fetal alcohol exposure alters neurosteroid levels in the developing rat brain.

    PubMed

    Caldeira, Jerri C; Wu, Yan; Mameli, Manuel; Purdy, Robert H; Li, Pui-Kai; Akwa, Yvette; Savage, Daniel D; Engen, John R; Valenzuela, C Fernando

    2004-09-01

    Neurosteroids are modulators of neuronal function that may play important roles in brain maturation. We determined whether chronic prenatal ethanol exposure altered neurosteroid levels in the developing brain. Rat dams were exposed to: (i) a 5% ethanol-containing liquid diet that produces peak maternal blood alcohol levels near the legal intoxication limit (approximately 0.08 g/dL); (ii) an isocaloric liquid diet containing maltose-dextrin instead of ethanol with pair-feeding; (iii) rat chow ad libitum. Neurosteroid levels were assessed in offspring brains using radioimmunoassay or gas chromatography-mass spectrometry techniques. A prenatal ethanol exposure-induced increase in pregnenolone sulfate levels, but not dehydroepiandrosterone sulfate levels, was evident at the earliest time point studied (embryonic day 14). This effect lasted until post-natal day 5. Levels of other neurosteroids were assessed at embryonic day 20; pregnenolone levels, but not allopregnanolone levels, were elevated. Pregnenolone sulfate levels were not altered in the maternal brain. Neither pregnenolone nor pregnenolone sulfate levels were significantly altered in the fetal liver, placenta and maternal blood, indicating that the effect of ethanol is not secondary to accumulation of peripherally-produced steroids. Fetal ethanol exposure has been shown to decrease both cellular and behavioral responsiveness to neurosteroids, and our findings provide a plausible explanation for this effect.

  13. Glutamatergic plasticity and alcohol dependence-induced alterations in reward, affect and cognition

    PubMed Central

    Burnett, Elizabeth J; Chandler, L Judson; Trantham-Davidson, Heather

    2015-01-01

    Introduction Alcohol dependence is characterized by a reduction in reward threshold, development of a negative affective state, and significant cognitive impairments. Dependence-induced glutamatergic neuroadaptations in the neurocircuitry mediating reward, affect and cognitive function are thought to underlie the neural mechanism for these alterations. These changes serve to promote increased craving for alcohol and facilitate the development of maladaptive behaviors that promote relapse to alcohol drinking during periods of abstinence. Objective To review the extant literature on the effects of chronic alcohol exposure on glutamatergic neurotransmission and its impact on reward, affect and cognition. Results Evidence from a diverse set of studies demonstrates significant enhancement of glutamatergic activity following chronic alcohol exposure and up-regulation of GluN2B-containing NMDA receptor expression and function is a commonly observed phenomenon that likely reflects activity-dependent adaptive homeostatic plasticity. However, changes in NMDA receptors and additional glutamatergic neuroadaptations are often circuit and cell-type specific. Discussion Dependence-induced alterations in glutamate signaling contribute to many of the symptoms experienced in addicted individuals and can persist well into abstinence. This suggests they play an important role in the development of behaviors that increase the probability for relapse. As our understanding of the complexity of the neurocircuitry involved in the addictive process has advanced, it has become increasingly clear that investigations of cell-type and circuit-specific effects are required to gain a more comprehensive understanding of the glutamatergic adaptations and their functional consequences in alcohol addiction. Conclusion While pharmacological treatments for alcohol dependence and relapse targeting the glutamatergic system have shown great promise in preclinical models, more research is needed to uncover

  14. Role of Ventral Subiculum in Context-Induced Relapse to Alcohol Seeking after Punishment-Imposed Abstinence

    PubMed Central

    Campbell, Erin J.; Whitaker, Leslie R.; Harvey, Brandon K.; Kaganovsky, Konstantin; Adhikary, Sweta; Hope, Bruce T.; Heins, Robert C.; Prisinzano, Thomas E.; Vardy, Eyal; Bonci, Antonello; Bossert, Jennifer M.

    2016-01-01

    In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive alcohol use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol drinking. We recently developed a rat model of this human condition in which we train alcohol-preferring P rats to self-administer alcohol in one context (A), punish the alcohol-reinforced responding in a different context (B), and then test for relapse to alcohol seeking in Contexts A and B without alcohol or shock. Here, we studied the role of projections to nucleus accumbens (NAc) shell from ventral subiculum (vSub), basolateral amygdala, paraventricular thalamus, and ventral medial prefrontal cortex in context-induced relapse after punishment-imposed abstinence. First, we measured double-labeling of the neuronal activity marker Fos with the retrograde tracer cholera toxin subunit B (injected in NAc shell) and demonstrated that context-induced relapse is associated with selective activation of the vSub→NAc shell projection. Next, we reversibly inactivated the vSub with GABA receptor agonists (muscimol+baclofen) before the context-induced relapse tests and provided evidence for a causal role of vSub in this relapse. Finally, we used a dual-virus approach to restrict expression of the inhibitory κ opioid-receptor based DREADD (KORD) in vSub→NAc shell projection neurons. We found that systemic injections of the KORD agonist salvinorin B, which selectively inhibits KORD-expressing neurons, decreased context-induced relapse to alcohol seeking. Our results demonstrate a critical role of vSub in context-induced relapse after punishment-imposed abstinence and further suggest a role of the vSub→NAc projection in this relapse. SIGNIFICANCE STATEMENT In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol

  15. Prenatal Alcohol Exposure Is Associated with Conduct Disorder in Adolescence: Findings from a Birth Cohort

    ERIC Educational Resources Information Center

    Larkby, Cynthia A.; Goldschmidt, Lidush; Hanusa, Barbara H.; Day, Nancy L.

    2011-01-01

    Objective: To evaluate the association between prenatal alcohol exposure and the rate of conduct disorder in exposed compared with unexposed adolescents. Method: Data for these analyses are from a longitudinal study of prenatal substance exposures. Women were interviewed at their fourth and seventh prenatal months, and with their children, at…

  16. Behavioral Outcomes of Young Children with Prenatal Exposure to Alcohol: Review and Analysis of Experimental Literature.

    ERIC Educational Resources Information Center

    Williams, Rosanne C.; Carta, Judith J.

    1996-01-01

    Analysis of 51 studies of developmental effects of prenatal exposure to alcohol in children from birth to 72 months found that, although adverse outcomes were found within each domain, age grouping, and exposure category, they comprised fewer than 50% of all outcomes measured. Most adverse outcomes were found in the neurobehavioral domain with…

  17. Adoption and Prenatal Alcohol and Drug Exposure: Research, Policy, and Practice.

    ERIC Educational Resources Information Center

    Barth, Richard P., Ed.; Freundlich, Madelyn, Ed.; Brodzinsky, David, Ed.

    As child welfare professionals have become aware of the impact of prenatal substance exposure on children in the adoption process or who are available for adoption, there is a heightened need for understanding a range of issues connected with prenatal alcohol and drug exposure. This book addresses many of these issues, including the impact of…

  18. Alcohol Use and Trauma Exposure among Male and Female Veterans Before, During, and After Military Service

    PubMed Central

    Kelley, Michelle L.; Runnals, Jennifer; Pearson, Matthew R.; Miller, Marinell; Fairbank, John A.; Brancu, Mira

    2017-01-01

    The present study examined lifespan and combat-related trauma exposure as predictors of alcohol use among male and female veterans. Posttraumatic stress and depressive symptoms were examined as mediators of the effects of trauma exposure on alcohol use. Data were examined from 1825 (1450 male, 375 female) veterans and active duty service members who took part in a multi-site research study conducted through the Department of Veterans Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Centers (VISN 6 MIRECC). For both men and women, depressive symptoms significantly mediated the effects of non-combat trauma exposure experienced before, during and after the military, as well as combat- exposure, on alcohol use. With posttraumatic stress symptoms, the models for men and women differed. For men, the effects of non-combat trauma exposure during and after military service, and combat exposure, on alcohol use were mediated by PTSD symptoms; however, for women, PTSD symptoms did not mediate these relationships. Findings are discussed in the context of potential gender differences in response to trauma such as use of alcohol to cope with traumatic events. PMID:24054989

  19. Prenatal marijuana and alcohol exposure and academic achievement at age 10.

    PubMed

    Goldschmidt, Lidush; Richardson, Gale A; Cornelius, Marie D; Day, Nancy L

    2004-01-01

    The effects of prenatal marijuana and alcohol exposure on school achievement at 10 years of age were examined. Women were interviewed about their substance use at the end of each trimester of pregnancy, at 8 and 18 months, and at 3, 6, 10, 14, and 16 years. The women were of lower socioeconomic status, high-school-educated, and light-to-moderate users of marijuana and alcohol. The sample was equally divided between Caucasian and African-American women. At the 10-year follow-up, the effects of prenatal exposure to marijuana or alcohol on the academic performance of 606 children were assessed. Exposure to one or more marijuana joints per day during the first trimester predicted deficits in Wide Range Achievement Test-Revised (WRAT-R) reading and spelling scores and a lower rating on the teachers' evaluations of the children's performance. This relation was mediated by the effects of first-trimester marijuana exposure on the children's depression and anxiety symptoms. Second-trimester marijuana use was significantly associated with reading comprehension and underachievement. Exposure to alcohol during the first and second trimesters of pregnancy predicted poorer teachers' ratings of overall school performance. Second-trimester binge drinking predicted lower reading scores. There was no interaction between prenatal marijuana and alcohol exposure. Each was an independent predictor of academic performance.

  20. Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior

    PubMed Central

    Vetreno, Ryan P.; Broadwater, Margaret A.; Robinson, Donita L.

    2016-01-01

    Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative–motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity

  1. Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior.

    PubMed

    Crews, Fulton T; Vetreno, Ryan P; Broadwater, Margaret A; Robinson, Donita L

    2016-10-01

    Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative-motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity to

  2. The Margin of Exposure of 5-Hydroxymethylfurfural (HMF) in Alcoholic Beverages

    PubMed Central

    Monakhova, Yulia B

    2012-01-01

    Objectives 5-Hydroxymethylfurfural (HMF) regularly occurs in foods and in alcoholic beverages. However, the risk of HMF associated with alcohol consumption has not been systematically studied, so that this study will provide the first quantitative risk assessment of HMF for consumers of alcoholic beverages. Methods Human dietary intake of HMF via alcoholic beverages in the European Union was estimated based on WHO alcohol consumption data combined with our own survey data (n=944) and literature data (n=147) about the HMF contents of different beverage groups (beer, wine, spirits and unrecorded alcohol). The risk assessment was conducted using the margin of exposure (MOE) approach. Results For olfactory epithelium metaplasia in female mice, a benchmark dose (BMD) of 127 mg/kg bodyweight (bw)/d and a BMD lower confidence limit (BMDL) of 79 mg/kg bw/d were calculated from National Toxicology Program oral long-term animal experiments. The average human exposure to HMF from alcoholic beverages was estimated at 6.0E-3 mg/kg bw/d, which is approximately 8.5% of the total dietary exposure. In comparison of the human exposure with BMDL, the MOE was 13,167 for average alcohol consumption scenarios, which is a value that would be generally assumed as safe for threshold based compounds. Conclusions The results show that the risk from HMF to the alcohol-consuming population is rather low and the priority for risk management (e.g. to reduce the contamination) is also low. Further toxicological research about HMF is required to further elucidate its mechanism. PMID:23106038

  3. Youth exposure to alcohol advertising on television--25 markets, United States, 2010.

    PubMed

    2013-11-08

    Excessive alcohol consumption accounted for an estimated 4,700 deaths and 280,000 years of potential life lost among youths aged <21 years each year during 2001-2005. Exposure to alcohol marketing increases the likelihood to varying degrees that youths will initiate drinking and drink at higher levels. By 2003, the alcohol industry voluntarily agreed not to advertise on television programs where >30% of the audience is reasonably expected to be aged <21 years. However, the National Research Council/Institute of Medicine (NRC/IOM) proposed in 2003 that "the industry standard should move toward a 15% threshold for television advertising". Because local media markets might have different age distributions, the Center on Alcohol Marketing and Youth, Johns Hopkins Bloomberg School of Public Health, evaluated the proportion of advertisements that appeared on television programs in 25 local television markets* and resulting youth exposure that exceeded the industry standard (i.e., >30% aged 2-20 years) or the proposed NRC/IOM standard (i.e., >15% aged 12-20 years). Among national television programs with alcohol advertising, placements were assessed for the 10 programs with the largest number of youth viewers within each of four program categories: network sports, network nonsports, cable sports, and cable nonsports (40 total). Of the 196,494 alcohol advertisements that aired on television programs with the largest number of youth viewers in these local markets, placement of 23.7% exceeded the industry threshold and 35.4% exceeded the NRC/IOM threshold. These results indicate that the alcohol industry's self-regulation of its advertising could be improved, and youth exposure to alcohol advertising could be further reduced by adopting and complying with the NRC/IOM standard. In addition, continued public health surveillance would allow for sustained assessment of youth exposure to alcohol advertising and inform future interventions.

  4. Restraint stress exacerbates alcohol-induced reproductive toxicity in male rats.

    PubMed

    Priya, P Hari; Girish, B P; Reddy, P Sreenivasula

    2014-12-01

    Cumulative exposure to multiple stresses may lead to aggravating the toxicity of each stress, qualitatively or quantitatively altering biological responses because of toxicological interaction. In this study, we intended to determine the possible effects of restraint stress on reproductive toxicity due to ethanol usage in male rats. Early pubertal male Wistar rats were subjected to either restraint stress (5 h/day) or alcohol intoxication (2 mg/kg body weight) or both for 60 days. Body weights of control and experimental rats were similar during the 60 days of this study. Testes were harvested, weighed, and prepared for enzyme assays, and cauda epididymides were isolated for the determination of density, motility, and viability of stored spermatozoa. Restraint stress or alcohol treatment significantly reduced testis weight and caused significant reductions in steroidogenesis and spermatogenesis. Mean density, motility, and viability of stored spermatozoa were reduced in experimental rats. Plasma testosterone concentrations in rats subjected to restraint stress or alcohol were decreased compared with those of controls, concomitant with increased concentrations of LH and FSH in experimental rats. These data suggest that sub-chronic exposure to restraint stress or alcohol contribute to reduce testicular and epididymal function in exposed rats. The study also suggests that restraint stress exacerbates alcohol-induced reproductive toxicity in rats.

  5. Vapor inhalation of alcohol in rats.

    PubMed

    Gilpin, Nicholas W; Richardson, Heather N; Cole, Maury; Koob, George F

    2008-07-01

    Alcohol dependence constitutes a neuroadaptive state critical for understanding alcoholism, and various methods have been utilized to induce alcohol dependence in animals, one of which is alcohol vapor exposure. Alcohol vapor inhalation provides certain advantages over other chronic alcohol exposure procedures that share the ultimate goal of producing alcohol dependence in rats. Chronic alcohol vapor inhalation allows the experimenter to control the dose, duration, and pattern of alcohol exposure. Also, this procedure facilitates testing of somatic and motivational aspects of alcohol dependence. Chronic exposure to alcohol vapor produces increases in alcohol-drinking behavior, increases in anxiety-like behavior, and reward deficits in rats. Alcohol vapor inhalation as a laboratory protocol is flexible, and the parameters of this procedure can be adjusted to accommodate the specific aims of different experiments. This unit describes the options available to investigators using this procedure for dependence induction, when different options are more or less appropriate, and the implications of each.

  6. Effects of pre-natal alcohol exposure on hippocampal synaptic plasticity: Sex, age and methodological considerations.

    PubMed

    Fontaine, Christine J; Patten, Anna R; Sickmann, Helle M; Helfer, Jennifer L; Christie, Brian R

    2016-05-01

    The consumption of alcohol during gestation is detrimental to the developing central nervous system (CNS). The severity of structural and functional brain alterations associated with alcohol intake depends on many factors including the timing and duration of alcohol consumption. The hippocampal formation, a brain region implicated in learning and memory, is highly susceptible to the effects of developmental alcohol exposure. Some of the observed effects of alcohol on learning and memory may be due to changes at the synaptic level, as this teratogen has been repeatedly shown to interfere with hippocampal synaptic plasticity. At the molecular level alcohol interferes with receptor proteins and can disrupt hormones that are important for neuronal signaling and synaptic plasticity. In this review we examine the consequences of prenatal and early postnatal alcohol exposure on hippocampal synaptic plasticity and highlight the numerous factors that can modulate the effects of alcohol. We also discuss some potential mechanisms responsible for these changes as well as emerging therapeutic avenues that are beginning to be explored.

  7. Ethanol exposure alters zebrafish development: a novel model of fetal alcohol syndrome.

    PubMed

    Bilotta, Joseph; Barnett, Jalynn A; Hancock, Laura; Saszik, Shannon

    2004-01-01

    Prenatal exposure to alcohol has been shown to produce the overt physical and behavioral symptoms known as fetal alcohol syndrome (FAS) in humans. Also, it is believed that low concentrations and/or short durations of alcohol exposure can produce more subtle effects. The purpose of this study was to investigate the effects of embryonic ethanol exposure on the zebrafish (Danio rerio) in order to determine whether this species is a viable animal model for studying FAS. Fertilized embryos were reared in varying concentrations of ethanol (1.5% and 2.9%) and exposure times (e.g., 0-8, 6-24, 12-24, and 48-72 h postfertilization; hpf); anatomical measures including eye diameter and heart rate were compared across groups. Results found that at the highest concentration of ethanol (2.9%), there were more abnormal physical distortions and significantly higher mortality rates than any other group. Embryos exposed to ethanol for a shorter duration period (0-8 hpf) at a concentration of 1.5% exhibited more subtle effects such as significantly smaller eye diameter and lower heart rate than controls. These results indicate that embryonic alcohol exposure affects external and internal physical development and that the severity of these effects is a function of both the amount of ethanol and the timing of ethanol exposure. Thus, the zebrafish represents a useful model for examining basic questions about the effects of embryonic exposure to ethanol on development.

  8. RE-AIM evaluation of the Alcohol and Pregnancy Project: educational resources to inform health professionals about prenatal alcohol exposure and fetal alcohol spectrum disorder.

    PubMed

    Payne, Janet M; France, Kathryn E; Henley, Nadine; D'Antoine, Heather A; Bartu, Anne E; O'Leary, Colleen M; Elliott, Elizabeth J; Bower, Carol; Geelhoed, Elizabeth

    2011-03-01

    The objective was to evaluate the Alcohol and Pregnancy Project that provided health professionals in Western Australia (WA) with educational resources to inform them about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder (FASD). The authors developed, produced, and distributed educational resources to 3,348 health professionals in WA. Six months later, they surveyed 1,483 of these health professionals. The authors used the RE-AIM framework (reach, effectiveness, adoption, implementation, and maintenance) to evaluate the project. The educational resources were effective in producing a 31% increase in the proportion of health professionals who routinely provided pregnant women with information about the consequences of drinking alcohol during pregnancy. One hundred percent of the settings adopted the project, it reached 96.3% of the target population, it was implemented as intended, and the resources were maintained (http://www.ichr.uwa.edu.au/alcoholandpregnancy). The educational resources for health professionals have potential to contribute to reducing prenatal alcohol exposure and FASD.

  9. Influence of extracellular calcium on allyl alcohol-induced hepatotoxicity.

    PubMed

    Strubelt, O; Younes, M; Pentz, R

    1986-07-01

    The role of calcium in allyl alcohol-induced hepatotoxicity was investigated in the isolated haemoglobin-free perfused rat liver. At a Ca++ concentration of 2.5 mmol/l in the perfusate, allyl alcohol (initial concentration 1.17 mmol/l) produced an enhanced release of GPT and SDH from the liver, an increase in the lactate/pyruvate ratio of the perfusate, a decrease in hepatic oxygen consumption and an increase of both hepatic calcium and malondialdehyde content. In the absence of Ca++ in the perfusate, no hepatic calcium accumulation occurred with allyl alcohol, but all other signs of hepatic damage were as severe as with 2.5 mmol/l Ca++. On the other hand, high extracellular Ca++ (5 mmol/l) alone led to a threefold increase of liver calcium but produced only marginal hepatotoxicity and only slightly enhanced the hepatotoxic effects of allyl alcohol. The concentrations of allyl alcohol in the perfusate were not altered at different Ca++ concentrations. In conclusion, the primary allyl alcohol-induced hepatotoxic injury does not appear to depend upon an influx of extracellular calcium.

  10. Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice

    PubMed Central

    Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

    2015-01-01

    We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure. PMID:25960751

  11. Metabolic and genetic factors contributing to alcohol induced effects and fetal alcohol syndrome.

    PubMed

    Gemma, Simonetta; Vichi, Susanna; Testai, Emanuela

    2007-01-01

    Alcohol-related damages on newborns and infants include a wide variety of complications from facial anomalies to neurodevelopmental delay, known as fetal alcohol syndrome (FAS). However, only less than 10% of women drinking alcohol during pregnancy have children with FAS. Understanding the risk factors increasing the probability for newborn exposed in utero to alcohol to develop FAS is therefore a key issue. The involvement of genetics as a one risk factor in FAS has been suggested by animal models and by molecular epidemiological studies on different populations, bearing allelic variants for those enzymes, such as ADH e CYP2E1, involved in ethanol metabolism. Indeed, one of the major factors determining the peak blood alcohol exposure to the fetus is the metabolic activity of the mother, in addition to placental and fetal metabolism, explaining, at least partially, the risk of FAS. The different rates of ethanol metabolism may be the result of genetic polymorphisms, the most relevant of which have been described in the paper.

  12. Central and Peripheral Timing Variability in Children with Heavy Prenatal Alcohol Exposure

    PubMed Central

    Simmons, Roger W.; Levy, Susan S.; Riley, Edward P.; Madra, Naju M.; Mattson, Sarah N.

    2008-01-01

    Background The study examined whether prenatal alcohol exposure is associated with increased motor timing variability when the timing response is partitioned into central clock variability, which indexes information processing at the central nervous system (CNS) level and motor delay variability, which reflects timing processes at the level of the peripheral nervous system (PNS). Methods Eighteen children with histories of prenatal alcohol exposure and 22 control children were assigned to young (7–11 years) or older (12–17 years) groups. Children tapped a single response key with the index finger in synchrony with a series of externally generated tones (the paced phase). At the conclusion of these tones, children continued tapping (the continuation phase) while attempting to maintain the same rate of tapping imposed by the paced phase. Two blocks of tapping were completed with inter-tone-intervals set at either 400 or 900 ms. Inter-response interval, central clock variability, and motor delay variability produced during the continuation phase were the dependent variables. Results Mean inter-response interval for the four groups did not differ for either time interval. Central clock variability produced by the young alcohol-exposed group was significantly greater than the two older groups for the 400 ms interval and all other groups for the 900 ms interval. Motor delay variability produced by the young alcohol-exposed group was significantly greater than the other three groups for both time intervals. Central and motor delay variability in children with and without alcohol exposure was directly related to the duration of the interval to be reproduced. Conclusions Central and peripheral timing variability was significantly greater for the young alcohol-exposed children. This atypical timing may be related to the teratogenic effects of alcohol, although the negative effects are limited to younger alcohol-exposed children since there were no differences in central

  13. Youth exposure to alcohol advertising in magazines--United States, 2001-2005.

    PubMed

    2007-08-03

    Alcohol consumption among persons aged 12-20 years contributes to the three leading causes of death (unintentional injury, homicide, and suicide) in this age group in the United States and is associated with other health-risk behaviors, including high-risk sexual activity, smoking, and physical fighting. Recent studies have documented the contribution of alcohol marketing to underage drinking. In 2000, the trade association for the wine industry changed its voluntary marketing code to stop advertising in magazines in which youths aged 12-20 years were >30% of the audience. In 2003, this threshold was adopted by the trade associations for beer and liquor producers. To determine the proportion of alcohol advertisements placed in magazines with disproportionately large youth readerships (i.e., >15% of readers aged 12-20 years) and to assess the proportion of youths exposed to these advertisements, the Center on Alcohol Marketing and Youth (Health Policy Institute, Georgetown University, District of Columbia) evaluated the placement of alcohol advertisements in 143 national magazines for which readership composition data were available for 2001-2005; these 143 publications accounted for approximately 90% of expenditures for all alcohol advertising in national print magazines. This report summarizes the results of that study, which indicated that alcohol advertising remained common in magazines with >15% youth readership but decreased substantially in magazines with >30% youth readership. These results suggest that although voluntary industry standards have reduced youth exposure to alcohol advertising in magazines, strengthening these standards by establishing a >15% youth readership threshold would further reduce exposure. In addition, independent monitoring of youth exposure to alcohol advertising should continue, as recommended by the U.S. Congress and Surgeon General.

  14. In vivo genotoxicity of alcohol consumption and lead exposure in printing press workers.

    PubMed

    Rajah, T T; Ahuja, Y R

    1996-01-01

    The objective of the present study was to evaluate the genotoxicity of a double exposure to alcohol and lead in subjects from the printing industry, and the possible interaction between the two agents. Individuals were classified into four different groups: controls, lead-exposed individuals, alcohol consumers, and lead-exposed alcohol consumers. Chromosomal analysis was carried out according to conventional methods and data on chromosome aberrations and sister chromatid exchanges (SCEs) were obtained for each individual. Alcohol consumers had a significant increase in the frequency of SCEs compared to the controls. Though there was an increase in the frequency of chromosome aberrations and SCEs in individuals exposed to lead, it was not significant. Statistical analysis did not reveal an interaction between alcohol and lead in either assay.

  15. Negative effects of curcumin on liver injury induced by alcohol.

    PubMed

    Zhao, Hai-Long; Song, Chang Ho; Chai, Ok Hee

    2012-12-01

    Curcumin is known for its antiinflammatory and antifibrotic properties in liver damage. However, the negative effects of curcumin on alcoholic liver damage are seldom reported. In this study, both advantageous and disadvantageous functions of curcumin on alcoholic liver injury were observed. In order to determine the effects of curcumin on liver fibrosis induced by alcohol, 5% ethanol and/or curcumin (1 × 10(-3) or 1 × 10(-4)  m) were injected intravenously in mice. Hematoxylin-eosin staining was performed to determine the value of liver injury by optical density analyses. Liver histology was evaluated by an experienced hepatopathologist blinded to the type of treatment received by the animals. Ethanol accelerates serum levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), liver injury, production of tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β) and nuclear factor-kappa B (NF-κB) during 5% ethanol-induced liver injury. 1 × 10(-3)  m curcumin accelerates liver injury and liver cellular edema during only 5% ethanol-induced liver injury evolution, whereas 1 × 10(-4)  m curcumin does not lead to (or protect) alcoholic liver injury. Therefore, it is suggested that curcumin may have dual effects on alcoholic liver injury depending on its concentration.

  16. Alcohol exposure in utero is associated with decreased gray matter volume in neonates.

    PubMed

    Donald, Kirsten A; Fouche, J P; Roos, Annerine; Koen, Nastassja; Howells, Fleur M; Riley, Edward P; Woods, Roger P; Zar, Heather J; Narr, Katherine L; Stein, Dan J

    2016-02-01

    Neuroimaging studies have indicated that prenatal alcohol exposure is associated with alterations in the structure of specific brain regions. However, the temporal specificity of such changes and their behavioral consequences are less known. Here we explore the brain structure of infants with in utero exposure to alcohol shortly after birth. T2 structural MRI images were acquired from 28 alcohol-exposed infants and 45 demographically matched healthy controls at 2-4 weeks of age on a 3T Siemens Allegra system as part of large birth cohort study, the Drakenstein Child Health Study (DCHS). Neonatal neurobehavior was assessed at this visit; early developmental outcome assessed on the Bayley Scales of Infant Development III at 6 months of age. Volumes of gray matter regions were estimated based on the segmentations of the University of North Carolina neonatal atlas. Significantly decreased total gray matter volume was demonstrated for the alcohol-exposed cohort compared to healthy control infants (p < 0.001). Subcortical gray matter regions that were significantly different between groups after correcting for overall gray matter volume included left hippocampus, bilateral amygdala and left thalamus (p < 0.01). These findings persisted even when correcting for infant age, gender, ethnicity and maternal smoking status. Both early neurobehavioral and developmental adverse outcomes at 6 months across multiple domains were significantly associated with regional volumes primarily in the temporal and frontal lobes in infants with prenatal alcohol exposure. Alcohol exposure during the prenatal period has potentially enduring neurobiological consequences for exposed children. These findings suggest the effects of prenatal alcohol exposure on brain growth is present very early in the first year of life, a period during which the most rapid growth and maturation occurs.

  17. Exposure to alcohol use in motion pictures and teen drinking in Latin America

    PubMed Central

    Mejia, Raul; Pérez, Adriana; Abad-Vivero, Erika N.; Kollath-Cattano, Christy; Gutierrez, Inti Barrientos; Thrasher, James F.; Sargent, James D.

    2015-01-01

    Objectives To assess whether exposure to alcohol use in films (AUF) is associated with alcohol use susceptibility, current alcohol use, and binge drinking in adolescents from two Latin American countries. Methods Cross-sectional study with 13,295 middle school students from public and private schools in Mexico and Argentina. Exposure to alcohol use in over 400 contemporary top box office films in each country was estimated using previously validated methods. Outcome measures included current drinking (i.e., any drink in the last 30 days), ever binge-drinking (i.e., more than 4 or 5 drinks in a row for females and males, respectively) and, among never drinkers, alcohol susceptibility (i.e., might drink in the next year or accept a drink from a friend). Multivariate models were adjusted for age, sex, parental education, peer drinking, sensation seeking, parenting style and media access. Results Mean age was 12.5 years (SD = 0.7) and the prevalence of alcohol consumption and binge drinking was 19.8% and 10.9% respectively. Mean exposure to alcohol from the film sample was about 7 hours in both countries. Adjusted models indicated independent dose-response associations between higher levels of exposure to AUF and all outcomes; the adjusted odds ratios (OR) comparing quartiles 4 and 1 1.99 (95% CI 1.73 - 2.30) for current drinking, 1.68 (1.39 - 2.02) for binge drinking, and 1.80 (1.52 - 2.12) for alcohol susceptibility. Compared to Mexican adolescents, Argentine adolescents were significantly more likely to have engaged in binge drinking (OR 1.40, 95% CI 1.12 - 1.76.) and, among never drinkers, were more susceptible to trying drinking (OR 1.40, 95% CI 1.20 - 1.64). Conclusions Higher levels of exposure to alcohol use in films was associated with higher likelihood of alcohol use, binge drinking, and alcohol susceptibility in Latin American adolescents. PMID:26857804

  18. Co-regulation of movement speed and accuracy by children with heavy prenatal alcohol exposure.

    PubMed

    Simmons, Roger W; Madra, Naju J; Levy, Susan S; Riley, Edward P; Mattson, Sarah N

    2011-02-01

    The study investigated how children with heavy prenatal alcohol exposure regulate movement speed and accuracy during goal-directed movements. 16 children ages 7 to 17 years with confirmed histories of heavy in utero alcohol exposure, and 21 nonalcohol-exposed control children completed a series of reciprocal tapping movements between two spatial targets. 5 different targets sets were presented, representing a range of task difficulty between 2 and 6 bits of information. Estimates of percent error rate, movement time, slope, and linear fit of the resulting curve confirmed that for goal-directed, reciprocal tapping responses, performance of the group with prenatal alcohol exposure was described by a linear function, as predicted by Fitts' law, by sacrificing movement accuracy. The index of performance was the same for the two groups: it initially increased, then leveled off for more difficult movements.

  19. Acute alcohol exposure markedly influences male fertility and fetal outcome in the male rat.

    PubMed

    Cicero, T J; Nock, B; O'Connor, L; Adams, M L; Sewing, B N; Meyer, E R

    1994-01-01

    Although it is recognized that drugs ingested by pregnant females produce marked cognitive and physiological deficits in their offspring, the possibility that paternal exposure to drugs prior to mating may have adverse effects on fertility and fetal outcome has not received much attention. The purpose of the present studies was to examine whether a single, acute exposure to alcohol influences the subsequent ability of adult male rats to mate and produce healthy and viable litters. Our results showed that a relatively large dose of alcohol 24 hours prior to breeding had little effect on the mating behavior of male rats, but there were markedly fewer pregnancies in females mated with alcohol-exposed male rats than in controls. Of equal importance, we found that, even when conception occurred and live births were produced, there were striking differences in fetal outcome. Alcohol-treated males sired many fewer pups than control males and there was a markedly enhanced mortality rate in their offspring. Collectively, these data suggest that acute paternal alcohol administration 24 hours prior to breeding does not affect mating behavior, but results in a greatly diminished fertility rate and fewer and less viable offspring. These studies suggest that paternal alcohol use may be as important as maternal alcohol abuse as a negative variable in pregnancy and fetal outcome.

  20. Perinatal aromatase activity in male and female rats: effect of prenatal alcohol exposure.

    PubMed

    McGivern, R F; Roselli, C E; Handa, R J

    1988-12-01

    Fetal alcohol exposure has been shown to produce long-term feminizing and demasculinizing effects on male rat behaviors which are organizationally dependent upon perinatal androgen levels. Such exposure has previously been shown to suppress the normal surge of testosterone during the critical prenatal period. Since defeminization of male rat behavior is dependent upon estrogen derived from the aromatization of testosterone in brain, brain aromatase activity was measured during the perinatal period in males and females exposed to alcohol beginning on Day 14 of gestation. Aromatase activity was measured in whole hypothalamus of fetuses from Day 16 through 20 of gestation and in the hypothalamic preoptic area and amygdala of animals 6-12 hr postparturition. Hypothalamic aromatase activity was elevated in fetal alcohol exposed males compared to controls on Days 18 and 19 of gestation and on postnatal Day 1. No effect of prenatal alcohol exposure was found in females. A sex effect in aromatase activity in the amygdala was evident on Day 1 when activity was found to be greater in males than females. Overall, these findings indicate that fetal alcohol exposure will elevate regional brain aromatase activity in males, but not females during the perinatal period of neurobehavioral sexual differentiation.

  1. Undernutrition Enhances Alcohol-Induced Hepatocyte Proliferation in the Liver of Rats Fed Via Total Enteral Nutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To assess the relative contributions of undernutrition and ethanol (EtOH) exposure to alcohol-induced hepatotoxicity, female Sprague-Dawley rats were intragastrically infused liquid diets containing 187 kcal/kg3/4/day or 154 kcal/kg3/4/day, with or without 11 g/kg/day EtOH. EtOH clearance was impai...

  2. Conceptualizing withdrawal-induced escalation of alcohol self-administration as a learned, plasticity-dependent process.

    PubMed

    Walker, Brendan M

    2012-06-01

    This article represents one of five contributions focusing on the topic "Plasticity and neuroadaptive responses within the extended amygdala in response to chronic or excessive alcohol exposure" that were developed by awardees participating in the Young Investigator Award Symposium at the "Alcoholism and Stress: A Framework for Future Treatment Strategies" conference in Volterra, Italy on May 3-6, 2011 that was organized/chaired by Drs. Antonio Noronha and Fulton Crews and sponsored by the National Institute on Alcohol Abuse and Alcoholism. This review discusses the dependence-induced neuroadaptations in affective systems that provide a basis for negative reinforcement learning and presents evidence demonstrating that escalated alcohol consumption during withdrawal is a learned, plasticity-dependent process. The review concludes by identifying changes within extended amygdala dynorphin/kappa-opioid receptor systems that could serve as the foundation for the occurrence of negative reinforcement processes. While some evidence contained herein may be specific to alcohol dependence-related learning and plasticity, much of the information will be of relevance to any addictive disorder involving negative reinforcement mechanisms. Collectively, the information presented within this review provides a framework to assess the negative reinforcing effects of alcohol in a manner that distinguishes neuroadaptations produced by chronic alcohol exposure from the actual plasticity that is associated with negative reinforcement learning in dependent organisms.

  3. Exposure to alcohol among adolescent students and associated factors

    PubMed Central

    Malta, Deborah Carvalho; Mascarenhas, Márcio Dênis Medeiros; Porto, Denise Lopes; Barreto, Sandhi Maria; de Morais, Otaliba Libânio

    2014-01-01

    OBJECTIVE To describe the prevalence of alcohol consumption among adolescent school students and identify its individual and contextual associated factors. METHODS The present research used data from the 2009 National School Health Survey (PeNSE), which included a sample of 59,699 9th grade students in Brazilian capitals and the Federal District. The association between regular alcohol consumption and independent explanatory variables was measured by means of the Pearson’s Chi-square test, with a 0.05 significance level. The explanatory variables were divided into four groups based on affinity (sociodemographic; school and family context; risk factors; and protection factors). A multivariate analysis was carried out for each group, always adjusting for age and sex. Variables with p < 0.10 were used in the final multivariate analysis model. RESULTS The highest alcohol consumption in the preceding 30 days was independently associated with pupils aged 15 years (OR = 1.46) and over, female (OR = 1.72), white, children of mothers with higher education, studying in private school, students who had tried smoking (OR = 1.72) and drug use (OR = 1.81), with regular tobacco consumption (OR = 2.16) and those who have had sexual intercourse (OR = 2.37). The factors related to family were skipping school without parental knowledge (OR = 1.49), parents not knowing what children do in their free time (OR = 1.34), having fewer meals with their parents (OR = 1.22), reporting that parents do not care (OR = 3.05), or care little (OR = 3.39) if they go home drunk, and having suffered domestic violence (OR = 1.36). CONCLUSIONS The results reinforce the importance of viewing alcohol consumption among adolescents as a complex, multifactorial and socially determined phenomenon. PMID:24789637

  4. Epigenetic Mechanisms in Developmental Alcohol-Induced Neurobehavioral Deficits

    PubMed Central

    Basavarajappa, Balapal S.; Subbanna, Shivakumar

    2016-01-01

    Alcohol consumption during pregnancy and its damaging consequences on the developing infant brain are significant public health, social, and economic issues. The major distinctive features of prenatal alcohol exposure in humans are cognitive and behavioral dysfunction due to damage to the central nervous system (CNS), which results in a continuum of disarray that is collectively called fetal alcohol spectrum disorder (FASD). Many rodent models have been developed to understand the mechanisms of and to reproduce the human FASD phenotypes. These animal FASD studies have provided several molecular pathways that are likely responsible for the neurobehavioral abnormalities that are associated with prenatal alcohol exposure of the developing CNS. Recently, many laboratories have identified several immediate, as well as long-lasting, epigenetic modifications of DNA methylation, DNA-associated histone proteins and microRNA (miRNA) biogenesis by using a variety of epigenetic approaches in rodent FASD models. Because DNA methylation patterns, DNA-associated histone protein modifications and miRNA-regulated gene expression are crucial for synaptic plasticity and learning and memory, they can therefore offer an answer to many of the neurobehavioral abnormalities that are found in FASD. In this review, we briefly discuss the current literature of DNA methylation, DNA-associated histone proteins modification and miRNA and review recent developments concerning epigenetic changes in FASD. PMID:27070644

  5. Adolescent alcohol exposure alters lysine demethylase 1 (LSD1) expression and histone methylation in the amygdala during adulthood.

    PubMed

    Kyzar, Evan J; Zhang, Huaibo; Sakharkar, Amul J; Pandey, Subhash C

    2016-05-15

    Alcohol exposure in adolescence is an important risk factor for the development of alcoholism in adulthood. Epigenetic processes are implicated in the persistence of adolescent alcohol exposure-related changes, specifically in the amygdala. We investigated the role of histone methylation mechanisms in the persistent effects of adolescent intermittent ethanol (AIE) exposure in adulthood. Adolescent rats were exposed to 2 g/kg ethanol (2 days on/off) or intermittent n-saline (AIS) during postnatal days (PND) 28-41 and used for behavioral and epigenetic studies. We found that AIE exposure caused a long-lasting decrease in mRNA and protein levels of lysine demethylase 1(Lsd1) and mRNA levels of Lsd1 + 8a (a neuron-specific splice variant) in specific amygdaloid structures compared with AIS-exposed rats when measured at adulthood. Interestingly, AIE increased histone H3 lysine 9 dimethylation (H3K9me2) levels in the central nucleus of the amygdala (CeA) and medial nucleus of the amygdala (MeA) in adulthood without producing any change in H3K4me2 protein levels. Acute ethanol challenge (2 g/kg) in adulthood attenuated anxiety-like behaviors and the decrease in Lsd1 + 8a mRNA levels in the amygdala induced by AIE. AIE caused an increase in H3K9me2 occupancy at the brain-derived neurotrophic factor exon IV promoter in the amygdala that returned to baseline after acute ethanol challenge in adulthood. These results indicate that AIE specifically modulates epizymes involved in H3K9 dimethylation in the amygdala in adulthood, which are possibly responsible for AIE-induced chromatin remodeling and adult psychopathology such as anxiety.

  6. Prenatal choline supplementation mitigates the adverse effects of prenatal alcohol exposure on development in rats.

    PubMed

    Thomas, Jennifer D; Abou, Elizabeth J; Dominguez, Hector D

    2009-01-01

    Prenatal alcohol exposure can lead to a range of physical, neurological, and behavioral alterations referred to as fetal alcohol spectrum disorders (FASD). Variability in outcome observed among children with FASD is likely related to various pre- and postnatal factors, including nutritional variables. Choline is an essential nutrient that influences brain and behavioral development. Recent animal research indicates that prenatal choline supplementation leads to long-lasting cognitive enhancement, as well as changes in brain morphology, electrophysiology and neurochemistry. The present study examined whether choline supplementation during ethanol exposure effectively reduces fetal alcohol effects. Pregnant dams were exposed to 6.0g/kg/day ethanol via intubation from gestational days (GD) 5-20; pair-fed and lab chow controls were included. During treatment, subjects from each group received choline chloride (250mg/kg/day) or vehicle. Physical development and behavioral development (righting reflex, geotactic reflex, cliff avoidance, reflex suspension and hindlimb coordination) were examined. Subjects prenatally exposed to alcohol exhibited reduced birth weight and brain weight, delays in eye opening and incisor emergence, and alterations in the development of all behaviors. Choline supplementation significantly attenuated ethanol's effects on birth and brain weight, incisor emergence, and most behavioral measures. In fact, behavioral performance of ethanol-exposed subjects treated with choline did not differ from that of controls. Importantly, choline supplementation did not influence peak blood alcohol level or metabolism, indicating that choline's effects were not due to differential alcohol exposure. These data indicate early dietary supplements may reduce the severity of some fetal alcohol effects, findings with important implications for children of women who drink alcohol during pregnancy.

  7. Lower risk for alcohol-induced cirrhosis in wine drinkers.

    PubMed

    Becker, Ulrik; Grønbaek, Morten; Johansen, Ditte; Sørensen, Thorkild I A

    2002-04-01

    Although there is a well-known relationship between total alcohol intake and future risk for cirrhosis, other factors such as the type of alcohol consumed are sparsely studied. The aim of this study was to assess the effects of wine compared with other types of alcoholic beverages on risk for alcohol-induced cirrhosis. In 3 prospective studies, 30,630 participants from the Copenhagen area were followed-up for a total observation time of 417,325 person-years. Information on weekly intake of beer, wine, and spirits, and sex, age, body mass index, smoking habits, and education was obtained from questionnaires. The primary outcome measures were first admission or death, with alcohol-induced cirrhosis obtained from death certificates and from the National Hospital Discharge Register. Data were analyzed by means of multiplicative Poisson regression models. We confirmed the increasing risk for cirrhosis with increasing alcohol intake. Individuals who drank more than 5 drinks per day had a relative risk of 14 to 20 for developing cirrhosis compared with non- or light drinkers. However, compared with individuals who drank no wine (relative risk set at 1.0), individuals drinking 16% to 30% wine of their total intake had a relative risk of 0.4 (95% confidence limits, 0.3-0.6) and those drinking 51% or more of wine had a relative risk of 0.3 (95% confidence limits, 0.2-0.5) for developing cirrhosis. In conclusion, the results suggest that a high intake of all 3 types of alcohol conveys an increased risk for cirrhosis, but wine drinkers are at a lower risk than beer and spirits drinkers.

  8. Driving simulator sickness: Impact on driving performance, influence of blood alcohol concentration, and effect of repeated simulator exposures.

    PubMed

    Helland, Arne; Lydersen, Stian; Lervåg, Lone-Eirin; Jenssen, Gunnar D; Mørland, Jørg; Slørdal, Lars

    2016-09-01

    Simulator sickness is a major obstacle to the use of driving simulators for research, training and driver assessment purposes. The purpose of the present study was to investigate the possible influence of simulator sickness on driving performance measures such as standard deviation of lateral position (SDLP), and the effect of alcohol or repeated simulator exposure on the degree of simulator sickness. Twenty healthy male volunteers underwent three simulated driving trials of 1h's duration with a curvy rural road scenario, and rated their degree of simulator sickness after each trial. Subjects drove sober and with blood alcohol concentrations (BAC) of approx. 0.5g/L and 0.9g/L in a randomized order. Simulator sickness score (SSS) did not influence the primary outcome measure SDLP. Higher SSS significantly predicted lower average speed and frequency of steering wheel reversals. These effects seemed to be mitigated by alcohol. Higher BAC significantly predicted lower SSS, suggesting that alcohol inebriation alleviates simulator sickness. The negative relation between the number of previous exposures to the simulator and SSS was not statistically significant, but is consistent with habituation to the sickness-inducing effects, as shown in other studies. Overall, the results suggest no influence of simulator sickness on SDLP or several other driving performance measures. However, simulator sickness seems to cause test subjects to drive more carefully, with lower average speed and fewer steering wheel reversals, hampering the interpretation of these outcomes as measures of driving impairment and safety. BAC and repeated simulator exposures may act as confounding variables by influencing the degree of simulator sickness in experimental studies.

  9. Impulsive Choice, Alcohol Consumption, and Pre-Exposure to Delayed Rewards: II. Potential Mechanisms

    PubMed Central

    Stein, Jeffrey S.; Renda, C. Renee; Hinnenkamp, Jay E.; Madden, Gregory J.

    2014-01-01

    In a prior study (Stein et al., 2013), we reported that rats pre-exposed to delayed rewards made fewer impulsive choices, but consumed more alcohol (12% wt/vol), than rats pre-exposed to immediate rewards. To understand the mechanisms that produced these findings, we again pre-exposed rats to either delayed (17.5 s; n = 32) or immediate (n = 30) rewards. In post-tests, delay-exposed rats made significantly fewer impulsive choices at both 15- and 30-s delays to a larger, later food reward than the immediacy-exposed comparison group. Behavior in an open-field test provided little evidence of differential stress exposure between groups. Further, consumption of either 12% alcohol or isocaloric sucrose in subsequent tests did not differ between groups. Because Stein et al. introduced alcohol concentration gradually (3–12%), we speculate that their group differences in 12% alcohol consumption were not determined by alcohol’s pharmacological effects, but by another variable (e.g., taste) that was preserved as an artifact from lower concentrations. We conclude that pre-exposure to delayed rewards generalizes beyond the pre-exposure delay; however, this same experimental variable does not robustly influence alcohol consumption. PMID:25418607

  10. Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P) Rats

    PubMed Central

    Godfrey, Jessica; Jeanguenin, Lisa; Castro, Norma; Olney, Jeffrey J.; Dudley, Jason; Pipkin, Joseph; Walls, Stanley M.; Wang, Wei; Herr, Deron R.; Harris, Greg L.; Brasser, Susan M.

    2015-01-01

    Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P) rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total) or were given access only to water (control). Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4)-desaturase (Degs2), an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels achieved by

  11. Hepatic cannabinoid receptor type 1 mediates alcohol-induced regulation of bile acid enzyme genes expression via CREBH.

    PubMed

    Chanda, Dipanjan; Kim, Yong-Hoon; Li, Tiangang; Misra, Jagannath; Kim, Don-Kyu; Kim, Jung Ran; Kwon, Joseph; Jeong, Won-Il; Ahn, Sung-Hoon; Park, Tae-Sik; Koo, Seung-Hoi; Chiang, John Y L; Lee, Chul-Ho; Choi, Hueng-Sik

    2013-01-01

    Bile acids concentration in liver is tightly regulated to prevent cell damage. Previous studies have demonstrated that deregulation of bile acid homeostasis can lead to cholestatic liver disease. Recently, we have shown that ER-bound transcription factor Crebh is a downstream effector of hepatic Cb1r signaling pathway. In this study, we have investigated the effect of alcohol exposure on hepatic bile acid homeostasis and elucidated the mediatory roles of Cb1r and Crebh in this process. We found that alcohol exposure or Cb1r-agonist 2-AG treatment increases hepatic bile acid synthesis and serum ALT, AST levels in vivo alongwith significant increase in Crebh gene expression and activation. Alcohol exposure activated Cb1r, Crebh, and perturbed bile acid homeostasis. Overexpression of Crebh increased the expression of key bile acid synthesis enzyme genes via direct binding of Crebh to their promoters, whereas Cb1r knockout and Crebh-knockdown mice were protected against alcohol-induced perturbation of bile acid homeostasis. Interestingly, insulin treatment protected against Cb1r-mediated Crebh-induced disruption of bile acid homeostasis. Furthermore, Crebh expression and activation was found to be markedly increased in insulin resistance conditions and Crebh knockdown in diabetic mice model (db/db) significantly reversed alcohol-induced disruption of bile acid homeostasis. Overall, our study demonstrates a novel regulatory mechanism of hepatic bile acid metabolism by alcohol via Cb1r-mediated activation of Crebh, and suggests that targeting Crebh can be of therapeutic potential in ameliorating alcohol-induced perturbation of bile acid homeostasis.

  12. Immediate and prolonged effects of alcohol exposure on the activity of the hypothalamic-pituitary-adrenal axis in adult and adolescent rats.

    PubMed

    Allen, Camryn D; Lee, Soon; Koob, George F; Rivier, Catherine

    2011-06-01

    Alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) axis. Part of this influence is likely exerted directly at the level of the corticotropin-releasing factor (CRF) gene, but intermediates may also play a role. Here we review the effect of alcohol on this axis, provide new data on the effects of binge drinking during adolescence, and argue for a role of catecholaminergic circuits. Indeed, acute injection of this drug activates brain stem adrenergic and noradrenergic circuits, and their lesion, or blockade of α1 adrenergic receptors significantly blunts alcohol-induced ACTH release. As alcohol can influence the HPA axis even once discontinued, and alcohol consumption in young people is associated with increased adult drug abuse (a phenomenon possibly mediated by the HPA axis), we determined whether alcohol consumption during adolescence modified this axis. The number of CRF-immunoreactive (ir) cells/section was significantly decreased in the central nucleus of the amygdala of adolescent self-administering binge-drinking animals, compared to controls. When another group of adolescent binge-drinking rats was administered alcohol in adulthood, the number of colocalized c-fos-ir and PNMT-ir cells/brain stem section in the C3 area was significantly decreased, compared to controls. As the HPA axis response to alcohol is blunted in adult rats exposed to alcohol vapors during adolescence, a phenomenon which was not observed in our model of self-administration, it is possible that the blood alcohol levels achieved in various models play a role in the long-term consequences of exposure to alcohol early in life. Collectively, these results suggest an important role of brain catecholamines in modulating the short- and long-term consequences of alcohol administration.

  13. Association between residential exposure to outdoor alcohol advertising and problem drinking among African American women in New York City.

    PubMed

    Kwate, Naa Oyo A; Meyer, Ilan H

    2009-02-01

    We evaluated the association between residential exposure to outdoor alcohol advertising and current problem drinking among 139 African American women aged 21 to 49 years in Central Harlem, New York City. We found that exposure to advertisements was positively related to problem drinking (13% greater odds), even after we controlled for a family history of alcohol problems and socioeconomic status. The results suggest that the density of alcohol advertisements in predominantly African American neighborhoods may add to problem drinking behavior of their residents.

  14. Moderate prenatal alcohol exposure and quantification of social behavior in adult rats.

    PubMed

    Hamilton, Derek A; Magcalas, Christy M; Barto, Daniel; Bird, Clark W; Rodriguez, Carlos I; Fink, Brandi C; Pellis, Sergio M; Davies, Suzy; Savage, Daniel D

    2014-12-14

    Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE(1), and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

  15. Alcohol-induced drying of carbon nanotubes and its implications for alcohol/water separation: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Tian, Xingling; Yang, Zaixing; Zhou, Bo; Xiu, Peng; Tu, Yusong

    2013-05-01

    Alcohols are important products in chemical industry, but separating them from their aqueous solutions is very difficult due to the hydrophilic nature of alcohols. Based on molecular dynamics simulations, we observe a striking nanoscale drying phenomenon and suggest an energy-saving and efficient approach toward alcohol/water separation by using single-walled carbon nanotubes (SWNTs). We use various common linear alcohols including C1-C6 1-alcohols and glycerol for demonstration (the phenol is also used as comparison). Our simulations show that when SWNTs are immersed in aqueous alcohols solutions, although the alcohols concentration is low (1 M), all kinds of alcohols can induce dehydration (drying) of nanotubes and accumulate inside wide [(13, 13)] and narrow [(6, 6) or (7, 7)] SWNTs. In particular, most kinds of alcohols inside the narrow SWNTs form nearly uniform 1D molecular wires. Detailed energetic analyses reveal that the preferential adsorption of alcohols over water inside nanotubes is attributed to the stronger dispersion interactions of alcohols with SWNTs than water. Interestingly, we find that for the wide SWNT, the selectivity for 1-alcohols increases with the number of alcohol's carbon atoms (Ncarbon) and exhibits an exponential law with respect to Ncarbon for C1-C5 1-alcohols; for narrow SWNTs, the selectivity for 1-alcohols is very high for methanol, ethanol, and propanol, and reaches a maximum when Ncarbon = 3. The underlying physical mechanisms and the implications of these observations for alcohol/water separation are discussed. Our findings provide the possibility for efficient dehydration of aqueous alcohols (and other hydrophilic organic molecules) by using SWNT bundles/membranes.

  16. Young Adults’ Exposure to Alcohol- and Marijuana-Related Content on Twitter

    PubMed Central

    Cabrera-Nguyen, E. Peter; Cavazos-Rehg, Patricia; Krauss, Melissa; Bierut, Laura J.; Moreno, Megan A.

    2016-01-01

    Objective: Twitter is among the most popular social media platforms used by young adults, yet it has been underutilized in substance use research compared with older platforms (e.g., MySpace and Facebook). We took a first step toward studying the associations between exposure to pro–alcohol- and marijuana-related content among young adults via Twitter and current heavy episodic drinking and current marijuana use, respectively. Method: We conducted an online survey of 587 (254 men, 333 women) Twitter users between ages 18 and 25 years in February 2014 using an online survey system that has been previously used in research on health behaviors and attitudes. Results: Current heavy episodic drinking was significantly associated with higher levels of exposure to pro-alcohol content. Similarly, current marijuana use was significantly associated with higher levels of exposure to pro-marijuana content. Conclusions: Our findings suggest that in-depth research regarding young adults’ exposure to pro–alcohol- and marijuana-related content via Twitter may provide a foundation for developing effective prevention messages on this social media platform to counter the pro–alcohol and marijuana messages. PMID:26997194

  17. Violence Exposure and Early Adolescent Alcohol Use: An Exploratory Study of Family Risk and Protective Factors

    ERIC Educational Resources Information Center

    Taylor, Kelli W.; Kliewer, Wendy

    2006-01-01

    In this short-term longitudinal exploratory interview study, the relations between exposure to community violence and subsequent alcohol use were examined, with a focus on caregiver and family variables as moderators. Maternal caregivers and their children (N = 101 families; 98% African American; M child age = 11.2 yrs) were interviewed separately…

  18. Assessing teratogenic changes in a zebrafish model of fetal alcohol exposure.

    PubMed

    Loucks, Evyn; Ahlgren, Sara

    2012-03-20

    Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to ethanol. It presents with characteristic defects to the face and organs, including mental retardation due to disordered and damaged brain development. Fetal alcohol spectrum disorder (FASD) is a term used to cover a continuum of birth defects that occur due to maternal alcohol consumption, and occurs in approximately 4% of children born in the United States. With 50% of child-bearing age women reporting consumption of alcohol, and half of all pregnancies being unplanned, unintentional exposure is a continuing issue. In order to best understand the damage produced by ethanol, plus produce a model with which to test potential interventions, we developed a model of developmental ethanol exposure using the zebrafish embryo. Zebrafish are ideal for this kind of teratogen study. Each pair lays hundreds of eggs, which can then be collected without harming the adult fish. The zebrafish embryo is transparent and can be readily imaged with any number of stains. Analysis of these embryos after exposure to ethanol at different doses and times of duration and application shows that the gross developmental defects produced by ethanol are consistent with the human birth defect. Described here are the basic techniques used to study and manipulate the zebrafish FAS model.

  19. Prologue: Understanding Children Who Have Been Affected by Maltreatment and Prenatal Alcohol Exposure

    ERIC Educational Resources Information Center

    Hyter, Yvette D.

    2007-01-01

    This prologue introduces an important topic for multiple disciplines involved with children and their families. This introduction includes a review of some of the current literature on the effects of maltreatment and prenatal alcohol exposure on child development, an explanation of why this topic is essential learning for communication…

  20. Effects of Chronic Alcohol Exposure on Kainate Receptor-Mediated Neurotransmission in the Hippocampus

    DTIC Science & Technology

    2002-09-01

    interneuronal KA-Rs. Moreover, a preliminary experiment with hippocampal slices from rats withdrawn from a 6-day inhalational exposure paradigm suggests...that the function of these receptors is upregulated. During the last year of support, we will concentrate on characterizing the function of KA-Rs in the CAl and CA3 regions in alcohol withdrawn rats.

  1. Children with heavy prenatal alcohol exposure have different frequency domain signal characteristics when producing isometric force.

    PubMed

    Nguyen, Tanya T; Ashrafi, Ashkan; Thomas, Jennifer D; Riley, Edward P; Simmons, Roger W

    2013-01-01

    To extend our current understanding of the teratogenic effects of prenatal alcohol exposure on the control of isometric force, the present study investigated the signal characteristics of power spectral density functions resulting from sustained control of isometric force by children with and without heavy prenatal exposure to alcohol. It was predicted that the functions associated with the force signals would be fundamentally different for the two groups. Twenty-five children aged between 7 and 17 years with heavy prenatal alcohol exposure and 21 non-alcohol exposed control children attempted to duplicate a visually represented target force by pressing on a load cell. The level of target force (5 and 20% of maximum voluntary force) and the time interval between visual feedback (20 ms, 320 ms and 740 ms) were manipulated. A multivariate spectral estimation method with sinusoidal windows was applied to individual isometric force-time signals. Analysis of the resulting power spectral density functions revealed that the alcohol-exposed children had a lower mean frequency, less spectral variability, greater peak power and a lower frequency at which peak power occurred. Furthermore, mean frequency and spectral variability produced by the alcohol-exposed group remained constant across target load and visual feedback interval, suggesting that these children were limited to making long-time scale corrections to the force signal. In contrast, the control group produced decreased mean frequency and spectral variability as target force and the interval between visual feedback increased, indicating that when feedback was frequently presented these children used the information to make short-time scale adjustments to the ongoing force signal. Knowledge of these differences could facilitate the design of motor rehabilitation exercises that specifically target isometric force control deficits in alcohol-exposed children.

  2. The CRHR1 gene, trauma exposure, and alcoholism risk: a test of G × E effects.

    PubMed

    Ray, L A; Sehl, M; Bujarski, S; Hutchison, K; Blaine, S; Enoch, M-A

    2013-06-01

    The corticotropin-releasing hormone type I receptor (CRHR1) gene has been implicated in the liability for neuropsychiatric disorders, particularly under conditions of stress. On the basis of the hypothesized effects of CRHR1 variation on stress reactivity, measures of adulthood traumatic stress exposure were analyzed for their interaction with CRHR1 haplotypes and single-nucleotide polymorphisms (SNPs) in predicting the risk for alcoholism. Phenotypic data on 2533 non-related Caucasian individuals (1167 alcoholics and 1366 controls) were culled from the publically available Study of Addiction: Genetics and Environment genome-wide association study. Genotypes were available for 19 tag SNPs. Logistic regression models examined the interaction between CRHR1 haplotypes/SNPs and adulthood traumatic stress exposure in predicting alcoholism risk. Two haplotype blocks spanned CRHR1. Haplotype analyses identified one haplotype in the proximal block 1 (P = 0.029) and two haplotypes in the distal block 2 (P = 0.026, 0.042) that showed nominally significant (corrected P < 0.025) genotype × traumatic stress interactive effects on the likelihood of developing alcoholism. The block 1 haplotype effect was driven by SNPs rs110402 (P = 0.019) and rs242924 (P = 0.019). In block 2, rs17689966 (P = 0.018) showed significant and rs173365 (P = 0.026) showed nominally significant, gene × environment (G × E) effects on alcoholism status. This study extends the literature on the interplay between CRHR1 variation and alcoholism, in the context of exposure to traumatic stress. These findings are consistent with the hypothesized role of the extra hypothalamic corticotropin-releasing factor system dysregulation in the initiation and maintenance of alcoholism. Molecular and experimental studies are needed to more fully understand the mechanisms of risk and protection conferred by genetic variation at the identified loci.

  3. Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms.

    PubMed

    Srinivasan, Padmanabhan; Kapadia, Rubina; Biswas, Arundhati; Said, Hamid M

    2014-11-01

    Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5'-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na(+) dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.

  4. Regulation of Milk Intake After Exposure to Alcohol in Mothers’ Milk

    PubMed Central

    Mennella, Julie A.

    2009-01-01

    Objective Contrary to the folklore which claims that drinking alcohol during lactation benefits both mother and infant, previous research in our laboratory revealed that breastfed infants consumed significantly less milk during the immediate hours after their mothers’ consumption of an alcoholic beverage. Because breastfed infants are clearly capable of regulating milk intake, the present study tested the hypothesis that infants would compensate for the diminished milk intake if their mothers then refrained from drinking alcohol. Methods A within-subjects design that controlled for time of day was implemented because of the great individual and daily variation in both milk composition and intake. To this end, 12 exclusively breastfed infants and their mothers were tested on 2 days separated by 1 week. Each woman drank a 0.3 g/kg dose of alcohol in orange juice on one testing day and orange juice alone on the other; the order was counterbalanced. The infants’ behaviors were monitored for the next 16 hr, the first 4 hr of monitoring on each test day occurred at the Monell Center. The infants fed on demand and immediately before and after each feeding, infants were weighed without a change in clothing. Results Consistent with previous findings, infants consumed significantly less milk during the 4 hr immediately after exposure to alcohol in mothers’ milk compared with the control condition. Compensatory increases in intake were then observed during the 8 to 16 hr after exposure when mothers refrained from drinking alcohol. Conclusions These findings demonstrate that short-term exposure to small amounts of alcohol in mothers’ milk produces distinctive changes in the infants’ patterns of feeding. PMID:11329500

  5. Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain.

    PubMed

    Ngai, Ying Fai; Sulistyoningrum, Dian C; O'Neill, Ryan; Innis, Sheila M; Weinberg, Joanne; Devlin, Angela M

    2015-09-01

    Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE.

  6. Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain

    PubMed Central

    Ngai, Ying Fai; Sulistyoningrum, Dian C.; O'Neill, Ryan; Innis, Sheila M.; Weinberg, Joanne

    2015-01-01

    Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE. PMID:26180184

  7. Alcohol Advertising at Boston Subway Stations: An Assessment of Exposure by Race and Socioeconomic Status

    PubMed Central

    Poirier, Katie; Wilkinson, Tiana; Nhean, Siphannay; Nyborn, Justin; Siegel, Michael

    2011-01-01

    Objectives. We investigated the frequency of alcohol ads at all 113 subway and streetcar stations in Boston and the patterns of community exposure stratified by race, socioeconomic status, and age. Methods. We assessed the extent of alcohol advertising at each station in May 2009. We measured gross impressions and gross rating points (GRPs) for the entire Greater Boston population and for Boston public school student commuters. We compared the frequency of alcohol advertising between neighborhoods with differing demographics. Results. For the Greater Boston population, alcohol advertising at subway stations generated 109 GRPs on a typical day. For Boston public school students in grades 5 to 12, alcohol advertising at stations generated 134 GRPs. Advertising at stations in low-poverty neighborhoods generated 14.1 GRPs and at stations in high-poverty areas, 63.6 GRPs. Conclusions. Alcohol ads reach the equivalent of every adult in the Greater Boston region and the equivalent of every 5th- to 12th-grade public school student each day. More alcohol ads were displayed in stations in neighborhoods with high poverty rates than in stations in neighborhoods with low poverty rates. PMID:21852632

  8. Experimentally induced anxiety attenuates alcohol-related aggression in men.

    PubMed

    Phillips, Joshua P; Giancola, Peter R

    2008-02-01

    The purpose of this study was to test the hypothesis that state anxiety operates as moderator of the alcohol-aggression relation. Participants were 80 healthy male social drinkers between 21 and 33 years of age. They were randomly assigned to 1 of 4 groups: (a) alcohol + anxiety induction (n = 20), (b) placebo + anxiety induction (n = 20), (c) alcohol + no anxiety induction (n = 20), and (d) placebo + no anxiety induction (n = 20). Anxiety was induced by informing participants that they had to deliver a speech about what they liked and disliked about their body in front of a video camera. A modified version of the Taylor Aggression Paradigm (S. Taylor, 1967) was then used to measure aggressive behavior in a situation where electric shocks were administered to, and received from, a fictitious opponent under the guise of a competitive reaction time task. Results indicated that the anxiety induction was successful in suppressing aggression for participants who received alcohol equal to levels seen in placebo controls. Findings are discussed within the context of a number of theories of alcohol's anxiolytic effects in relation to intoxicated aggression.

  9. Prenatal alcohol and other early childhood adverse exposures: Direct and indirect pathways to adolescent drinking

    PubMed Central

    Cornelius, Marie D.; De Genna, Natacha M.; Goldschmidt, Lidush; Larkby, Cynthia; Day, Nancy L.

    2016-01-01

    We examined direct and indirect pathways between adverse environmental exposures during gestation and childhood and drinking in mid-adolescence. Mothers and their offspring (n = 917 mother/child dyads) were followed prospectively from second trimester to a 16-year follow-up assessment. Interim assessments occurred at delivery, 6, 10, and 14 years. Adverse environmental factors included gestational exposures to alcohol, tobacco, and marijuana, exposures to childhood maltreatment and violence, maternal psychological symptoms, parenting practices, economic and home environments, and demographic characteristics of the mother and child. Indirect effects of early child behavioral characteristics including externalizing, internalizing activity, attention, and impulsivity were also examined. Polytomous logistic regression analyses were used to evaluate direct effects of adverse environmental exposures with level of adolescent drinking. Structural equation modeling (SEM) was applied to simultaneously estimate the relation between early adversity variables, childhood characteristics, and drinking level at age 16 while controlling for significant covariates. Level of drinking among the adolescent offspring was directly predicted by prenatal exposure to alcohol, less parental strictness, and exposures to maltreatment and violence during childhood. Whites and offspring with older mothers were more likely to drink at higher levels. There was a significant indirect effect between childhood exposure to violence and adolescent drinking via childhood externalizing behavior problems. All other hypothesized indirect pathways were not significant. Thus most of the early adversity measures directly predicted adolescent drinking and did not operate via childhood behavioral dysregulation characteristics. These results highlight the importance of adverse environmental exposures on pathways to adolescent drinking. PMID:26994529

  10. Assessment of Exposure to Alcohol Vapor from Alcohol-Based Hand Rubs

    PubMed Central

    Bessonneau, Vincent; Thomas, Olivier

    2012-01-01

    This study assessed the inhaled dose of alcohol during hand disinfection. Experiments were conducted with two types of hand rub using two hand disinfection procedures. Air samples were collected every 10 s from the breathing zone, by bubbling through a mixture of K2Cr2O7 and H2SO4. The reduction of dichromate ions in the presence of alcohols was followed by UV-vis spectrophotometry. The difference in intensity of the dichromate absorption peak was used to quantify the alcohol concentration expressed in ethanol equivalent. During hygienic hand disinfection, the mean ethanol equivalent concentrations peaked at around 20–30 s for both hand rubs (14.3 ± 1.4 mg/L for hand rub 1 and 13.2 ± 0.7 mg/L for hand rub 2). During surgical hand disinfection, two peaks were found at the same time (40 and 80 s) for both hand rubs. The highest mean concentrations were 20.2 ± 0.9 mg/L for hand rub 1 and 18.1 ± 0.9 mg/L for hand rub 2. For hand rub 1, the total absorbed doses, calculated from ethanol with an inhalation flow of 24 L/min and an absorption rate of 62%, were 46.5 mg after one hygienic hand disinfection and 203.9 mg after one surgical hand disinfection. Although the use of ABHRs leads to the absorption of very low doses, sudden, repeated inhalation of high alcohol concentrations raises the question of possible adverse health effects. PMID:22690169

  11. Assessment of exposure to alcohol vapor from alcohol-based hand rubs.

    PubMed

    Bessonneau, Vincent; Thomas, Olivier

    2012-03-01

    This study assessed the inhaled dose of alcohol during hand disinfection. Experiments were conducted with two types of hand rub using two hand disinfection procedures. Air samples were collected every 10 s from the breathing zone, by bubbling through a mixture of K(2)Cr(2)O(7) and H(2)SO(4). The reduction of dichromate ions in the presence of alcohols was followed by UV-vis spectrophotometry. The difference in intensity of the dichromate absorption peak was used to quantify the alcohol concentration expressed in ethanol equivalent. During hygienic hand disinfection, the mean ethanol equivalent concentrations peaked at around 20-30 s for both hand rubs (14.3 ± 1.4 mg/L for hand rub 1 and 13.2 ± 0.7 mg/L for hand rub 2). During surgical hand disinfection, two peaks were found at the same time (40 and 80 s) for both hand rubs. The highest mean concentrations were 20.2 ± 0.9 mg/L for hand rub 1 and 18.1 ± 0.9 mg/L for hand rub 2. For hand rub 1, the total absorbed doses, calculated from ethanol with an inhalation flow of 24 L/min and an absorption rate of 62%, were 46.5 mg after one hygienic hand disinfection and 203.9 mg after one surgical hand disinfection. Although the use of ABHRs leads to the absorption of very low doses, sudden, repeated inhalation of high alcohol concentrations raises the question of possible adverse health effects.

  12. Role of microRNAs in Alcohol-Induced Multi-Organ Injury

    PubMed Central

    Natarajan, Sathish Kumar; Pachunka, Joseph M.; Mott, Justin L.

    2015-01-01

    Alcohol consumption and its abuse is a major health problem resulting in significant healthcare cost in the United States. Chronic alcoholism results in damage to most of the vital organs in the human body. Among the alcohol-induced injuries, alcoholic liver disease is one of the most prevalent in the United States. Remarkably, ethanol alters expression of a wide variety of microRNAs that can regulate alcohol-induced complications or dysfunctions. In this review, we will discuss the role of microRNAs in alcoholic pancreatitis, alcohol-induced liver damage, intestinal epithelial barrier dysfunction, and brain damage including altered hippocampus structure and function, and neuronal loss, alcoholic cardiomyopathy, and muscle damage. Further, we have reviewed the role of altered microRNAs in the circulation, teratogenic effects of alcohol, and during maternal or paternal alcohol consumption. PMID:26610589

  13. In utero exposure to alcohol and puberty in boys: a pregnancy cohort study

    PubMed Central

    Håkonsen, Linn Berger; Brath-Lund, Mette Louise; Hounsgaard, Marie Louise; Olsen, Jørn; Ernst, Andreas; Thulstrup, Ane Marie; Bech, Bodil Hammer; Ramlau-Hansen, Cecilia Høst

    2014-01-01

    Objectives Epidemiological studies have raised concerns about the reproductive consequences of in utero exposure to alcohol. Maternal lifestyle factors have been associated with altered pubertal development, but the impact of prenatal alcohol exposure on male puberty is unknown. Thus, the objective was to explore whether prenatal alcohol exposure alters pubertal development in boys. Setting Follow-up of a Danish pregnancy cohort. Participants Sons (N=2522) of women who were enrolled in a Danish pregnancy cohort between 1984 and 1987. Primary and secondary outcome measures Indicators of pubertal development, assessed by age at first nocturnal emission, voice break, acne and regular shaving. Results We found a tendency towards a later age at first nocturnal emission and voice break following in utero exposure to binge drinking. Boys exposed to ≥5 binge drinking episodes during pregnancy experienced their first nocturnal emission 7.3 months (95% CI −2.8 to 17.4) later and voice break 4.9 months (95% CI −0.6 to 10.4) later than the unexposed boys. Results for average weekly alcohol consumption were in the same direction, but differences were smaller and not statistically significant. Conclusions We found no strong support for the hypothesis that in utero exposure to weekly alcohol consumption is a risk factor for altered pubertal development, but a tendency towards delayed pubertal development among boys exposed to binge drinking during fetal life was observed. Longitudinal studies, with data collected as children go through puberty, are needed to explore this further. PMID:24916086

  14. Gender differences in alcohol-induced neurotoxicity and brain damage.

    PubMed

    Alfonso-Loeches, Silvia; Pascual, María; Guerri, Consuelo

    2013-09-06

    Considerable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1β, TNF-α), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse.

  15. Protection of Xenopus laevis embryos against alcohol-induced delayed gut maturation and growth retardation by peroxiredoxin 5 and catalase.

    PubMed

    Peng, Ying; Yang, Pai-Hao; Ng, Samuel S M; Lum, Ching Tung; Kung, Hsiang-Fu; Lin, Marie C

    2004-07-16

    Accumulated evidence indicates that maternal alcohol consumption causes fetal enteric damage and growth retardation. In this study, we investigated the underlying molecular mechanisms in a Xenopus model of fetal alcohol exposure. We established a condition of transient alcohol exposure that produces tadpoles with delayed gut maturation and decreased body length. We then investigated the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) by microinjecting plasmids expressing catalase and peroxiredoxin 5 (PRDX5) into two-cell stage embryos. Finally, the effects of these enzymes on the expression of key gut developmental genes were determined by animal cap explant assay. We showed that exposure of Xenopus embryos to 0.5% alcohol from stage 13 to stage 22 produced tadpoles with delayed gut maturation, reduced growth, and down-regulation in several gut developmental genes, with VegT, Pax6 and Sox17 most vulnerable. We further demonstrated that microinjection of catalase attenuated alcohol-induced ROS production and restored the expression of VegT and Pax6, but protected the embryos from delayed gut development and retarded growth only partially. By contrast, microinjection of PRDX5 reduced both ROS and RNS production, and prevented the gut and growth defects, and restored VegT, Pax6 and Sox17 gene expression. A positive correlation was found between delayed gut maturation and reduced body length. These results indicate the crucial roles of both the ROS-Pax6 and RNS-Sox17 signaling axes in alcohol-induced fetal gut defects and growth retardation. In addition, they suggest strongly a cause-and-effect relationship between alcohol-induced delayed gut maturation and growth retardation.

  16. Is It Important to Prevent Early Exposure to Drugs and Alcohol Among Adolescents?

    PubMed Central

    Odgers, Candice L.; Caspi, Avshalom; Nagin, Daniel S.; Piquero, Alex R.; Slutske, Wendy S.; Milne, Barry J.; Dickson, Nigel; Poulton, Richie; Moffitt, Terrie E.

    2013-01-01

    Exposure to alcohol and illicit drugs during early adolescence has been associated with poor outcomes in adulthood. However, many adolescents with exposure to these substances also have a history of conduct problems, which raises the question of whether early exposure to alcohol and drugs leads to poor outcomes only for those adolescents who are already at risk. In a 30-year prospective study, we tested whether there was evidence that early substance exposure can be a causal factor for adolescents’ future lives. After propensity-score matching, early-exposed adolescents remained at an increased risk for a number of poor outcomes. Approximately 50% of adolescents exposed to alcohol and illicit drugs prior to age 15 had no conduct-problem history, yet were still at an increased risk for adult substance dependence, herpes infection, early pregnancy, and crime. Efforts to reduce or delay early substance exposure may prevent a wide range of adult health problems and should not be restricted to adolescents who are already at risk. PMID:19000215

  17. p53 pathway determines the cellular response to alcohol-induced DNA damage in MCF-7 breast cancer cells

    PubMed Central

    Zhao, Ming; Howard, Erin W.; Guo, Zhiying; Parris, Amanda B.; Yang, Xiaohe

    2017-01-01

    Alcohol consumption is associated with increased breast cancer risk; however, the underlying mechanisms that contribute to mammary tumor initiation and progression are unclear. Alcohol is known to induce oxidative stress and DNA damage; likewise, p53 is a critical modulator of the DNA repair pathway and ensures genomic integrity. p53 mutations are frequently detected in breast and other tumors. The impact of alcohol on p53 is recognized, yet the role of p53 in alcohol-induced mammary carcinogenesis remains poorly defined. In our study, we measured alcohol-mediated oxidative DNA damage in MCF-7 cells using 8-OHdG and p-H2AX foci formation assays. p53 activity and target gene expression after alcohol exposure were determined using p53 luciferase reporter assay, qPCR, and Western blotting. A mechanistic study delineating the role of p53 in DNA damage response and cell cycle arrest was based on isogenic MCF-7 cells stably transfected with control (MCF-7/Con) or p53-targeting siRNA (MCF-7/sip53), and MCF-7 cells that were pretreated with Nutlin-3 (Mdm2 inhibitor) to stabilize p53. Alcohol treatment resulted in significant DNA damage in MCF-7 cells, as indicated by increased levels of 8-OHdG and p-H2AX foci number. A p53-dependent signaling cascade was stimulated by alcohol-induced DNA damage. Moderate to high concentrations of alcohol (0.1–0.8% v/v) induced p53 activation, as indicated by increased p53 phosphorylation, reporter gene activity, and p21/Bax gene expression, which led to G0/G1 cell cycle arrest. Importantly, compared to MCF-7/Con cells, alcohol-induced DNA damage was significantly enhanced, while alcohol-induced p21/Bax expression and cell cycle arrest were attenuated in MCF-7/sip53 cells. In contrast, inhibition of p53 degradation via Nutlin-3 reinforced G0/G1 cell cycle arrest in MCF-7 control cells. Our study suggests that functional p53 plays a critical role in cellular responses to alcohol-induced DNA damage, which protects the cells from DNA damage

  18. Alcohol-induced alterations in dopamine modulation of prefrontal activity.

    PubMed

    Trantham-Davidson, Heather; Chandler, L Judson

    2015-12-01

    Long-term alcohol use leads to persistent cognitive deficits that may be associated with maladaptive changes in the neurocircuitry that mediates executive functions. Impairments caused by these changes can persist well into abstinence and have a negative impact on quality of life and job performance, and can increase the probability of relapse. Many of the changes that affect cognitive function appear to involve dysregulation of the mesocortical dopamine system. This includes changes in dopamine release and alterations in dopamine receptor expression and function in the medial prefrontal cortex (PFC). This review summarizes the cellular effects of acute and chronic ethanol exposure on dopamine release and dopamine receptor function in the PFC with the goal of providing greater understanding of the effects of alcohol-use disorders on the dopamine system and how this relates to deficits in the executive function of the PFC.

  19. Alcohol-induced alterations in dopamine modulation of prefrontal activity

    PubMed Central

    Trantham-Davidson, Heather; Chandler, L. Judson

    2015-01-01

    Long-term alcohol use leads to persistent cognitive deficits that may be associated with maladaptive changes in the neurocircuitry that mediates executive functions. Impairments caused by these changes can persist well into abstinence and have a negative impact on quality of life and job performance, and can increase the probability of relapse. Many of the changes that affect cognitive function appear to involve dysregulation of the mesocortical dopamine system. This includes changes in dopamine release and alterations in dopamine receptor expression and function in the medial prefrontal cortex (PFC). This review summarizes the cellular effects of acute and chronic ethanol exposure on dopamine release and dopamine receptor function in the PFC with the goal of providing greater understanding of the effects of alcohol-use disorders on the dopamine system and how this relates to deficits in the executive function of the PFC. PMID:26558348

  20. Hippocampal Neuron Populations Are Reduced in Vervet Monkeys With Fetal Alcohol Exposure

    PubMed Central

    Burke, Mark W; Ptito, Maurice; Ervin, Frank R; Palmour, Roberta M

    2015-01-01

    Prenatal exposure to beverage alcohol is a major cause of mild mental retardation and developmental delay. In nonendangered alcohol-preferring vervet monkeys, we modeled the most common nondysmorphic form of fetal alcohol syndrome disorder with voluntary drinking during the third trimester of pregnancy. Here, we report significant numerical reductions in the principal hippocampal neurons of fetal alcohol-exposed (FAE) offspring, as compared to age-matched, similarly housed conspecifics with isocaloric sucrose exposure. These deficits, particularly marked in CA1 and CA3, are present neonatally and persist through infancy (5 months) and juvenile (2 years) stages. Although the volumes of hippocampal subdivisions in FAE animals are not atypical at birth, by age 2, they are only 65–70% of those estimated in age-matched controls. These data suggest that moderate, naturalistic alcohol consumption during late pregnancy results in a stable loss of hippocampal neurons and a progressive reduction of hippocampal volume. © 2015 The Authors. Developmental Psychobiology Published by Wiley Periodicals, Inc. Dev Psychobiol 57:470–485, 2015. PMID:25913787

  1. Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood.

    PubMed

    Parker, Matthew O; Evans, Alexandra M-D; Brock, Alistair J; Combe, Fraser J; Teh, Muy-Teck; Brennan, Caroline H

    2016-01-01

    Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and μ-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning.

  2. Effect of gestational ethanol exposure on parvalbumin and calretinin expressing hippocampal neurons in a chick model of fetal alcohol syndrome.

    PubMed

    Marshall, Audrey G; McCarthy, Molly M; Brishnehan, Kirk M; Rao, Venugopal; Batia, Lyn M; Gupta, Madhul; Das, Srijit; Mitra, Nilesh K; Chaudhuri, Joydeep D

    2009-03-01

    Fetal alcohol syndrome (FAS), a condition occurring in some children of mothers who have consumed alcohol during pregnancy, is characterized by physical deformities and learning and memory deficits. The chick hippocampus, whose functions are controlled by interneurons expressing calcium-binding proteins parvalbumin (PV) and calretinin (CR), is involved in learning and memory mechanisms. Effects on growth and development and hippocampal morphology were studied in chick embryos exposed to 5% and 10% ethanol volume/volume (vol/vol) for 2 or 8 days of gestation. There was a significant dose-dependent reduction (P<.05) in body weight and mean number per section of PV and CR expressing hippocampal neurons in ethanol-exposed chicks, without alterations in neuronal nuclear size or hippocampal volume, compared appropriate controls. Moreover, when chicks exposed to 5% ethanol for 2 and 8 days of gestation were compared, no significant differences were found in body parameters or neuronal counts. Similarly, exposure to 10% ethanol did not induce any significant changes in chicks exposed for 2 or 8 gestational days. Thus, these results suggest that gestational ethanol exposure induces a reduction in the mean number per section of PV and CR expressing hippocampal neurons, and could be a possible mechanism responsible for learning and memory disorders in FAS.

  3. Effects of alcohol exposure during development on play behavior and c-Fos expression in response to play behavior

    PubMed Central

    Lawrence, R. Charles; Bonner, H. Cale; Newsom, Ryan J.; Kelly, Sandra J.

    2008-01-01

    Developmental exposure to alcohol can produce characteristic physiological and cognitive deficits, often termed Fetal Alcohol Spectrum Disorder (FASD). More recently, social deficits have been shown to occur both in FASD and animal models of FASD; the behavioral and neural bases of these deficits remain to be determined. It was hypothesized that changes in sensory processing may in part underlie the social deficits seen in FASD. This study used a rat model of FASD and social play, a behavior critical to adult social functioning, to begin to examine this hypothesis. Somatosensory cues from dorsal contact to the nape of the neck, critical to the initiation of pinning, were systematically degraded by administration of different doses of xylocaine, a topical anesthetic. Neuronal activity after one hour of play was assessed by measurement of c-Fos immunoreactivity (IR) in different brain regions. Ethanol-exposed rats showed an increase frequency of pinning during social play and were more sensitive to the degradation of somatosensory cues compared to the control groups, suggesting difficulties in processing somatosensory cues. Neuronal activity in the somatosensory cortex induced by play was significantly decreased in the ethanol-exposed group compared to the non-treated group. The c-Fos IR in the nucleus accumbens was altered in a sexually dimorphic manner in the ethanol-exposed group. Thus, the behavioral and brain measures are consistent with the hypothesis that ethanol exposure during development induces alterations in social play via deficits in processing somatosensory cues that are important to social play. PMID:18160143

  4. Resveratrol Ameliorates Alcoholic Fatty Liver by Inducing Autophagy.

    PubMed

    Tang, Liying; Yang, Fengli; Fang, Zhirui; Hu, Chengmu

    2016-01-01

    Alcoholic fatty liver (AFL) is early stage of alcoholic liver disease, which can progress to steatohepatitis, fibrosis, and cirrhosis if alcohol consumption is continued. The pathogenesis of AFL is associated with excessive lipid accumulation in hepatocytes. Resveratrol (RES), a dietary polyphenol found in red wines and grapes, has been shown to have a hepatoprotective effect. Autophagy is a crucial physiological process in cellular catabolism that involves the regulation of lipid droplets. Autophagy maintains a balance between protein synthesis, degradation and self-recycling. In the present study, we evaluated the protective effects of RES (10[Formula: see text]mg/kg, 30[Formula: see text]mg/kg, 100[Formula: see text]mg/kg) on AFL mice fed with an ethanol Lieber-DeCarli liquid diet, and HepG2 cells in the presence of oleic acid and alcohol to investigate whether resveratrol could induce autophagy to attenuate lipid accumulation. The results showed that RES (30[Formula: see text]mg/kg and 100[Formula: see text]mg/kg) treatment significantly attenuated hepatic steatosis and lowered the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), low density lipoprotein cholesterol (LDL-C). H&E staining showed that RES reduced hepatic lipid accumulation. Transmission electron microscopy (TEM) images showed that RES treatment increased the number of autophagosomes and promoted the formation of autophagy. Western blot analysis showed that RES treatment increased the levels of microtubule-associated protein light chain3- II (LC3-II) and Beclin1, decreased expression of p62 protein. In addition, in vitro studies also demonstrated that RES led to the formation of acidic vesicular organelles (AVOs), however, 3-Methyladenine (3-MA), a specific inhibitor of autophagy, obviously inhibited the above effects of RES. In conclusion, RES has protective effects on alcoholic hepatic steatosis, and the potential mechanism might be involved

  5. Development of brain vessels in human embryos and fetuses in conditions of prenatal exposure to alcohol.

    PubMed

    Solonskii, A V; Logvinov, S V; Kutepova, N A

    2008-05-01

    Light and electron microscopy were used to study the characteristics of the formation of brain vascular structures at the early stages of development in conditions of maternal alcoholization during pregnancy. Computer morphometric methods using the Scion Image system for image analysis showed that fetuses at 11-12 weeks of development in conditions of prenatal alcohol exposure showed a decrease in the mean absolute cross-sectional area of vessels in the intermediate layer of the brain, with an increase in their relative area and an increase per unit area of sections, as compared with the control group. Vessels started to differentiate into arteries and veins from 10 weeks of development.

  6. Prenatal exposure to alcohol affects the ability to maintain postural balance.

    PubMed

    Roebuck, T M; Simmons, R W; Mattson, S N; Riley, E P

    1998-02-01

    Prenatal exposure to alcohol is known to affect gross motor functioning. Animal studies have shown that balance is particularly affected, and there is some evidence that similar deficits exist in alcohol-exposed children. In the current study, postural balance, or the ability to maintain equilibrium, was assessed in a group of alcohol-exposed children (ALC group; n = 11) and controls (NC group; n = 11) individually matched for age and sex. Balance was measured across six conditions designed to systematically manipulate or eliminate visual or somatosensory information. Equilibrium and strategy scores for each condition and a derived composite balance score were analyzed. Although the ALC group had a lower mean composite balance score, their performance was similar to that of the NC group on all conditions where somatosensory input was reliable. However, when somatosensory input was manipulated, and when both somatosensory and visual input were inaccurate, the ALC group performed more poorly than controls. Interestingly, there were no differences between the ALC group and NC group in the type of control strategy used to maintain balance. These results suggest that alcohol-exposed children are overly reliant on somatosensory input. When this input is atypical, alcohol-exposed children display significantly greater anterior-posterior body sway and are unable to compensate using available visual or vestibular information. These deficits may be related to cerebellar anomalies previously reported in fetal alcohol syndrome children.

  7. Alcohol

    MedlinePlus

    ... that's how many accidents occur. continue What Is Alcoholism? What can be confusing about alcohol is that ... develop a problem with it. Sometimes, that's called alcoholism (say: al-kuh-HOL - ism) or being an ...

  8. Alcohol

    MedlinePlus

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  9. Long-term genomic and epigenomic dysregulation as a consequence of prenatal alcohol exposure: a model for fetal alcohol spectrum disorders

    PubMed Central

    Kleiber, Morgan L.; Diehl, Eric J.; Laufer, Benjamin I.; Mantha, Katarzyna; Chokroborty-Hoque, Aniruddho; Alberry, Bonnie; Singh, Shiva M.

    2014-01-01

    There is abundant evidence that prenatal alcohol exposure leads to a range of behavioral and cognitive impairments, categorized under the term fetal alcohol spectrum disorders (FASDs). These disorders are pervasive in Western cultures and represent the most common preventable source of neurodevelopmental disabilities. The genetic and epigenetic etiology of these phenotypes, including those factors that may maintain these phenotypes throughout the lifetime of an affected individual, has become a recent topic of investigation. This review integrates recent data that has progressed our understanding FASD as a continuum of molecular events, beginning with cellular stress response and ending with a long-term “footprint” of epigenetic dysregulation across the genome. It reports on data from multiple ethanol-treatment paradigms in mouse models that identify changes in gene expression that occur with respect to neurodevelopmental timing of exposure and ethanol dose. These studies have identified patterns of genomic alteration that are dependent on the biological processes occurring at the time of ethanol exposure. This review also adds to evidence that epigenetic processes such as DNA methylation, histone modifications, and non-coding RNA regulation may underlie long-term changes to gene expression patterns. These may be initiated by ethanol-induced alterations to DNA and histone methylation, particularly in imprinted regions of the genome, affecting transcription which is further fine-tuned by altered microRNA expression. These processes are likely complex, genome-wide, and interrelated. The proposed model suggests a potential for intervention, given that epigenetic changes are malleable and may be altered by postnatal environment. This review accentuates the value of mouse models in deciphering the molecular etiology of FASD, including those processes that may provide a target for the ammelioration of this common yet entirely preventable disorder. PMID:24917881

  10. Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice

    PubMed Central

    Robins, Meridith T.; Lu, Julie

    2016-01-01

    The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61) exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations. PMID:27380261

  11. Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice.

    PubMed

    Robins, Meridith T; Lu, Julie; van Rijn, Richard M

    2016-01-01

    The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61) exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations.

  12. Effects of low-dose alcohol exposure on simulated merchant ship piloting by maritime cadets.

    PubMed

    Howland, J; Rohsenow, D J; Cote, J; Gomez, B; Mangione, T W; Laramie, A K

    2001-03-01

    The US Department of Transportation (DOT) regulates on-the-job alcohol use by operators of certain categories of commercial transport. For aircraft, trains, and commercial vessels, operators are subject to sanctions for having > or = 0.04 g% blood alcohol concentration (BAC). This study examines the effects of alcohol (between 0.04 and 0.05 g% BAC) on simulated merchant ship handling. A two-group randomized factorial design was used to compare beverage alcohol to placebo while controlling for baseline performance on a previous day. The study was conducted in the Maritime Simulation Center at Maine Maritime Academy, Castine, ME. Participants were 38 volunteer deck officer cadets in their junior or senior year, at least 21 years of age, with previous experience on a bridge simulator. Following a baseline trial on Day 1, on Day 2 participants were randomized to receive alcohol (0.6 g/kg for males and 0.5 g/kg for females) or placebo. After allowing time for absorption, participants completed a bridge simulator task. For baseline and performance trials, participants were randomized to one of four bridge simulator scenarios, each representing passage of a fully loaded container vessel through a channel with commercial traffic. The aggregate scenario score given by blinded maritime educators measured performance. A main effect for alcohol was found indicating that performance was significantly impaired by this low dose of alcohol relative to performance in the placebo condition. These findings are consistent with current federal regulations that limit low-dose alcohol exposure for the operators of commercial transport vehicles. Further research is required to determine effects at lower BACs.

  13. Adolescent alcohol exposure and persistence of adolescent-typical phenotypes into adulthood: a mini-review

    PubMed Central

    Spear, Linda Patia; Swartzwelder, H. Scott

    2014-01-01

    Alcohol use is typically initiated during adolescence, which, along with young adulthood, is a vulnerable period for the onset of high-risk drinking and alcohol abuse. Given across-species commonalities in certain fundamental neurobehavioral characteristics of adolescence, studies in laboratory animals such as the rat have proved useful to assess persisting consequences of repeated alcohol exposure. Despite limited research to date, reports of long-lasting effects of adolescent ethanol exposure are emerging, along with certain common themes. One repeated finding is that adolescent exposure to ethanol sometimes results in the persistence of adolescent-typical phenotypes into adulthood. Instances of adolescent -like persistence have been seen in terms of baseline behavioral, cognitive, electrophysiological and neuroanatomical characteristics, along with the retention of adolescent-typical sensitivities to acute ethanol challenge. These effects are generally not observed after comparable ethanol exposure in adulthood. Persistence of adolescent-typical phenotypes is not always evident, and may be related to regionally-specific ethanol influences on the interplay between CNS excitation and inhibition critical for the timing of neuroplasticity. PMID:24813805

  14. Adolescent alcohol exposure and persistence of adolescent-typical phenotypes into adulthood: a mini-review.

    PubMed

    Spear, Linda Patia; Swartzwelder, H Scott

    2014-09-01

    Alcohol use is typically initiated during adolescence, which, along with young adulthood, is a vulnerable period for the onset of high-risk drinking and alcohol abuse. Given across-species commonalities in certain fundamental neurobehavioral characteristics of adolescence, studies in laboratory animals such as the rat have proved useful to assess persisting consequences of repeated alcohol exposure. Despite limited research to date, reports of long-lasting effects of adolescent ethanol exposure are emerging, along with certain common themes. One repeated finding is that adolescent exposure to ethanol sometimes results in the persistence of adolescent-typical phenotypes into adulthood. Instances of adolescent-like persistence have been seen in terms of baseline behavioral, cognitive, electrophysiological and neuroanatomical characteristics, along with the retention of adolescent-typical sensitivities to acute ethanol challenge. These effects are generally not observed after comparable ethanol exposure in adulthood. Persistence of adolescent-typical phenotypes is not always evident, and may be related to regionally specific ethanol influences on the interplay between CNS excitation and inhibition critical for the timing of neuroplasticity.

  15. Alcohol-induced serotonergic modulation: the role of histone deacetylases.

    PubMed

    Agudelo, Marisela; Yoo, Changwon; Nair, Madhavan P

    2012-11-01

    Previous studies have demonstrated that alcohol use disorders (AUDs) are regulated by multiple mechanisms such as neurotransmitters and enzymes. The neurotransmitter, serotonin (5-hydroxytryptamine, 5-HT) may contribute to alcohol effects and serotonin receptors, including 5-HT3, play an important role in AUDs. Recent studies have also implicated histone deacetylases (HDACs) and acetyltransferases (HATS) in regulation of drug addiction, and HDAC inhibitors (HDACi) have been reported as transcriptional modulators of monoaminergic neurotransmission. Therefore, we hypothesize that HDACs may play a role in ethanol-induced serotonergic modulation. The effects of ethanol on serotonin and 5-HT3, and the role HDACs, HDAC activity and the HDACi, trichostatin A (TSA), play in alcohol-induced serotonergic effects were studied. Human SK-N-MC and neurons, were treated with ethanol (0.05, 0.1 and 0.2%), and/or TSA (50 nM), and 5-HT3 levels were assessed at 24-72 h. Gene expression was evaluated by qRT-PCR and protein by western blot and flow cytometry. Serotonin release was assessed by ELISA and HDAC activity by fluorometric assay. Our results show an increase in 5-HT3 gene after ethanol treatment. Further, ethanol significantly increased HDACs 1 and 3 genes accompanied by an increased in HDAC activity while TSA significantly inhibited HDACs. Studies with TSA show a significant upregulation of ethanol effects on 5-HT3, while surprisingly TSA inhibited ethanol-induced serotonin production. These results suggest that ethanol affects 5-HT3 and serotonin through mechanisms involving HDACs and HATs. In summary, our studies demonstrate some of the novel properties of HDAC inhibitors and contribute to the understanding of the mechanisms involve in alcohol-serotonergic modulation in the CNS.

  16. Alcohol vapor exposure differentially impacts mesocorticolimbic cytokine expression in a sex-, region-, and duration-specific manner.

    PubMed

    Baxter-Potter, Lydia N; Henricks, Angela M; Berger, Anthony L; Bieniasz, Kennedy V; Lugo, Janelle M; McLaughlin, Ryan J

    2017-03-27

    Alcohol exposure elicits the production of cytokines that regulate the host response to infection, immunity, inflammation, and trauma. Although increased production of pro-inflammatory cytokines has been linked to symptoms of alcoholism, few studies have evaluated whether cytokine expression changes across the development of alcohol dependence, or whether these changes are region and/or sex specific. In the present study, we subjected adult male and female rats to different regimens of alcohol vapor exposure (acute, subchronic, or chronic) and measured relative mRNA expression for tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and chemokine (C-C motif) ligand 2 (CCL2) in reward-related brain regions. Results indicated that acute alcohol exposure increased TNFα mRNA expression in the basolateral amygdala (BLA), nucleus accumbens (NAc), and ventral tegmental area (VTA), whereas IL-6 expression was increased in the VTA, NAc, and ventromedial prefrontal cortex (vmPFC) only in males. After subchronic exposure (1week daily intermittent exposure, 14h on:10h off), TNFα expression remained elevated in the BLA, NAc, and VTA, while IL-6 expression was reduced in the male vmPFC. Chronic alcohol exposure (6week daily intermittent exposure, 14 h on: 10 h off) increased TNFα mRNA expression in the NAc and increased IL-6 mRNA in the vmPFC and NAc. Interestingly, chronic alcohol exposure also robustly increased CCL2 mRNA expression in the BLA and VTA in males but not females. Thus, alcohol vapor exposure elicits sex-, region-, and duration-specific cytokine alterations that may contribute to differences in the manifestation and progression of symptoms of alcohol dependence in male and female populations.

  17. Voluntary exercise partially reverses neonatal alcohol-induced deficits in mPFC layer II/III dendritic morphology of male adolescent rats.

    PubMed

    Hamilton, G F; Criss, K J; Klintsova, A Y

    2015-08-01

    Developmental alcohol exposure in humans can produce a wide range of deficits collectively referred to as fetal alcohol spectrum disorders (FASD). FASD-related impairments in executive functioning later in life suggest long-term damage to the prefrontal cortex (PFC). In rodent neonates, moderate to high levels of alcohol exposure decreased frontal lobe brain size and altered medial PFC pyramidal neuron dendritic morphology. Previous research in our lab demonstrated that neonatal alcohol exposure decreased basilar dendritic complexity but did not affect spine density in Layer II/III pyramidal neurons in 26- to 30-day-old rats. The current study adds to the literature by evaluating the effect of neonatal alcohol exposure on mPFC Layer II/III basilar dendritic morphology in adolescent male rats. Additionally, it examines the potential for voluntary exercise to mitigate alcohol-induced deficits on mPFC dendritic complexity. An animal model of binge drinking during the third trimester of pregnancy was used. Rats were intubated with alcohol (alcohol-exposed, AE; 5.25 g kg(-1) day(-1)) on postnatal days (PD) 4-9; two control groups were included (suckle control and sham-intubated). Rats were anesthetized and perfused with heparinized saline solution on PD 42, and brains were processed for Golgi-Cox staining. Developmental alcohol exposure decreased spine density and dendritic complexity of basilar dendrites of Layer II/III neurons in the medial PFC (mPFC) compared to dendrites of control animals. Voluntary exercise increased spine density and dendritic length in AE animals resulting in elimination of the differences between AE and SH rats. Thus, voluntary exercise during early adolescence selectively rescued alcohol-induced morphological deficits in the mPFC.

  18. Differentiating prenatal exposure to methamphetamine and alcohol versus alcohol and not methamphetamine using tensor-based brain morphometry and discriminant analysis.

    PubMed

    Sowell, Elizabeth R; Leow, Alex D; Bookheimer, Susan Y; Smith, Lynne M; O'Connor, Mary J; Kan, Eric; Rosso, Carly; Houston, Suzanne; Dinov, Ivo D; Thompson, Paul M

    2010-03-17

    Here we investigate the effects of prenatal exposure to methamphetamine (MA) on local brain volume using magnetic resonance imaging. Because many who use MA during pregnancy also use alcohol, a known teratogen, we examined whether local brain volumes differed among 61 children (ages 5-15 years), 21 with prenatal MA exposure, 18 with concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but not MA exposure (ALC group), and 27 unexposed controls. Volume reductions were observed in both exposure groups relative to controls in striatal and thalamic regions bilaterally and in right prefrontal and left occipitoparietal cortices. Striatal volume reductions were more severe in the MAA group than in the ALC group, and, within the MAA group, a negative correlation between full-scale intelligence quotient (FSIQ) scores and caudate volume was observed. Limbic structures, including the anterior and posterior cingulate, the inferior frontal gyrus (IFG), and ventral and lateral temporal lobes bilaterally, were increased in volume in both exposure groups. Furthermore, cingulate and right IFG volume increases were more pronounced in the MAA than ALC group. Discriminant function analyses using local volume measurements and FSIQ were used to predict group membership, yielding factor scores that correctly classified 72% of participants in jackknife analyses. These findings suggest that striatal and limbic structures, known to be sites of neurotoxicity in adult MA abusers, may be more vulnerable to prenatal MA exposure than alcohol exposure and that more severe striatal damage is associated with more severe cognitive deficit.

  19. Comparative risk assessment of carcinogens in alcoholic beverages using the margin of exposure approach.

    PubMed

    Lachenmeier, Dirk W; Przybylski, Maria C; Rehm, Jürgen

    2012-09-15

    Alcoholic beverages have been classified as carcinogenic to humans. As alcoholic beverages are multicomponent mixtures containing several carcinogenic compounds, a quantitative approach is necessary to compare the risks. Fifteen known and suspected human carcinogens (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, lead, 4-methylimidazole, N-nitrosodimethylamine, ochratoxin A and safrole) occurring in alcoholic beverages were identified based on monograph reviews by the International Agency for Research on Cancer. The margin of exposure (MOE) approach was used for comparative risk assessment. MOE compares a toxicological threshold with the exposure. MOEs above 10,000 are judged as low priority for risk management action. MOEs were calculated for different drinking scenarios (low risk and heavy drinking) and different levels of contamination for four beverage groups (beer, wine, spirits and unrecorded alcohol). The lowest MOEs were found for ethanol (3.1 for low risk and 0.8 for heavy drinking). Inorganic lead and arsenic have average MOEs between 10 and 300, followed by acetaldehyde, cadmium and ethyl carbamate between 1,000 and 10,000. All other compounds had average MOEs above 10,000 independent of beverage type. Ethanol was identified as the most important carcinogen in alcoholic beverages, with clear dose response. Some other compounds (lead, arsenic, ethyl carbamate, acetaldehyde) may pose risks below thresholds normally tolerated for food contaminants, but from a cost-effectiveness point of view, the focus should be on reducing alcohol consumption in general rather than on mitigative measures for some contaminants that contribute only to a limited extent (if at all) to the total health risk.

  20. Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation.

    PubMed

    Gan, Gabriela; Sterzer, Philipp; Marxen, Michael; Zimmermann, Ulrich S; Smolka, Michael N

    2015-12-01

    Although alcohol consumption is linked to increased aggression, its neural correlates have not directly been studied in humans so far. Based on a comprehensive neurobiological model of alcohol-induced aggression, we hypothesized that alcohol-induced aggression would go along with increased amygdala and ventral striatum reactivity and impaired functioning of the prefrontal cortex (PFC) under alcohol. We measured neural and behavioral correlates of alcohol-induced aggression in a provoking vs non-provoking condition with a variant of the Taylor aggression paradigm (TAP) allowing to differentiate between reactive (provoked) and proactive (unprovoked) aggression. In a placebo-controlled cross-over design with moderate alcohol intoxication (~0.6 g/kg), 35 young healthy adults performed the TAP during functional magnetic resonance imaging (fMRI). Analyses revealed that provoking vs non-provoking conditions and alcohol vs placebo increased aggression and decreased brain responses in the anterior cingulate cortex/dorso-medial PFC (provokingalcoholalcohol specifically increased proactive (unprovoked) but not reactive (provoked) aggression (alcohol × provocation interaction). However, investigation of inter-individual differences revealed (1) that pronounced alcohol-induced proactive aggression was linked to higher levels of aggression under placebo, and (2) that pronounced alcohol-induced reactive aggression was related to increased amygdala and ventral striatum reactivity under alcohol, providing evidence for their role in human alcohol-induced reactive aggression. Our findings suggest that in healthy young adults a liability for alcohol-induced aggression in a non-provoking context might depend on overall high levels of aggression, but on alcohol-induced increased striatal and amygdala reactivity when triggered by provocation.

  1. Alcohol

    MedlinePlus

    ... de los dientes Video: Getting an X-ray Alcohol KidsHealth > For Kids > Alcohol Print A A A What's in this article? ... What Is Alcoholism? Say No en español El alcohol Getting the Right Message "Hey, who wants a ...

  2. Developmental alcohol exposure leads to a persistent change on astrocyte secretome.

    PubMed

    Trindade, Pablo; Hampton, Brian; Manhães, Alex C; Medina, Alexandre E

    2016-06-01

    Fetal alcohol spectrum disorder is the most common cause of mental disabilities in the western world. It has been quite established that acute alcohol exposure can dramatically affect astrocyte function. Because the effects of early alcohol exposure on cell physiology can persist into adulthood, we tested the hypothesis that ethanol exposure in ferrets during a period equivalent to the last months of human gestation leads to persistent changes in astrocyte secretome in vitro. Animals were treated with ethanol (3.5 g/kg) or saline between postnatal day (P)10-30. At P31, astrocyte cultures were made and cells were submitted to stable isotope labeling by amino acids. Twenty-four hour conditioned media of cells obtained from ethanol- or saline-treated animals (ET-CM or SAL-CM) were collected and analyzed by quantitative mass spectrometry in tandem with liquid chromatography. Here, we show that 65 out of 280 quantifiable proteins displayed significant differences comparing ET-CM to SAL-CM. Among the 59 proteins that were found to be reduced in ET-CM we observed components of the extracellular matrix such as laminin subunits α2, α4, β1, β2, and γ1 and the proteoglycans biglycan, heparan sulfate proteoglycan 2, and lumican. Proteins with trophic function such as insulin-like growth factor binding protein 4, pigment epithelium-derived factor, and clusterin as well as proteins involved on modulation of proteolysis such as metalloproteinase inhibitor 1 and plasminogen activator inhibitor-1 were also reduced. In contrast, pro-synaptogeneic proteins like thrombospondin-1, hevin as well as the modulator of extracelular matrix expression, angiotensinogen, were found increased in ET-CM. The analysis of interactome maps through ingenuity pathway analysis demonstrated that the amyloid beta A4 protein precursor, which was found reduced in ET-CM, was previously shown to interact with ten other proteins that exhibited significant changes in the ET-CM. Taken together our results

  3. Altered Hepatic Transport by Fetal Arsenite Exposure in Diet-Induced Fatty Liver Disease.

    PubMed

    Ditzel, Eric J; Li, Hui; Foy, Caroline E; Perrera, Alec B; Parker, Patricia; Renquist, Benjamin J; Cherrington, Nathan J; Camenisch, Todd D

    2016-07-01

    Non-alcoholic fatty liver disease can result in changes to drug metabolism and disposition potentiating adverse drug reactions. Furthermore, arsenite exposure during development compounds the severity of diet-induced fatty liver disease. This study examines the effects of arsenite potentiated diet-induced fatty liver disease on hepatic transport in male mice. Changes were detected for Mrp2/3/4 hepatic transporter gene expression as well as for Oatp1a4/2b1/1b2. Plasma concentrations of Mrp and Oatp substrates were increased in arsenic exposure groups compared with diet-only controls. In addition, murine embryonic hepatocytes and adult primary hepatocytes show significantly altered transporter expression after exposure to arsenite alone: a previously unreported phenomenon. These data indicate that developmental exposure to arsenite leads to changes in hepatic transport which could increase the risk for ADRs during fatty liver disease.

  4. Neuropsychological comparison of children with heavy prenatal alcohol exposure and an IQ-matched comparison group.

    PubMed

    Vaurio, Linnea; Riley, Edward P; Mattson, Sarah N

    2011-05-01

    An objective in current research on children with fetal alcohol spectrum disorders (FASD) is to determine neurobehavioral profiles to identify affected individuals. Deficits observed when children with FASD are compared to typically developing controls may be confounded by lower IQ scores in the subjects with FASD. To determine if prenatal alcohol exposure is associated with neurobehavioral deficits after controlling for IQ differences, multivariate analyses were conducted to compare alcohol-exposed (ALC) subjects to a comparison group closely matched on IQ (IQC). The initial analysis included a broad neuropsychological battery with measures of language, executive function, visual-motor integration, motor ability, and academic achievement. Additional, in depth comparisons focused on visual sustained attention, verbal learning and memory and parent/guardian-reported behavior problems. Group differences (ALC < IQC) were found on verbal learning and parent-rated behavior problems. Group differences were marginally significant (measures within the broad neuropsychological comparison) or not significant (visual attention, retention of verbal material) on the remaining comparisons. Therefore, some deficits (e.g., verbal learning and behavior problems) in children with heavy prenatal alcohol exposure cannot be explained by the lower FSIQ observed in the population. These areas of relative weakness could be useful in distinguishing children with FASD from other children with lowered IQ.

  5. Risk for Exposure to Alcohol, Tobacco, and Other Drugs on the Route to and from School: The Role of Alcohol Outlets

    PubMed Central

    Milam, AJ; Furr-Holden, CDM; Cooley-Strickland, MC; Bradshaw, CP; Leaf, PJ

    2013-01-01

    Despite the national push encouraging children to walk to school, little work has been done to examine what hazards children encounter on the route to school. This study examined the association between the presence of alcohol outlets on children’s route to school and perceived safety on the route to school as well as exposure to alcohol, tobacco, and other drugs (ATOD). Data come from a community-based epidemiological study of 394 urban elementary school students. Participants’ residential address, school location, and alcohol outlet data were geocoded and the route to school was mapped. The route to school layer and the geocoded alcohol outlet data were joined to determine the number of alcohol outlets children pass on the route to school. Logistic regression models estimated the association between the presence of alcohol outlets on the route to school, alcohol and drug exposure, and self-reported safety. Children with an alcohol outlet on the route to school were more likely to be offered ATOD (OR= 2.20, p=.02) as well as be exposed to drug selling (OR=1.72, p=.02) and seeing people using drugs (OR=1.93, p=.02). After adjusting for individual-level variables the relationship between presence of alcohol outlets and being offered ATOD and seeing people using drugs remained significant. However, after adjusting for individual-level control variables and a proxy for the larger neighborhood context, the association between the presence of alcohol outlets and exposure to ATOD was no longer significant. As national campaigns are encouraging children to walk to school it is essential to consider what children are exposed to on the route to school. PMID:23408286

  6. Youth Alcohol Brand Consumption and Exposure to Brand Advertising in Magazines

    PubMed Central

    Ross, Craig S; Ostroff, Joshua; Siegel, Michael B; DeJong, William; Naimi, Timothy S; Jernigan, David H

    2014-01-01

    Objective: Recently published research has identified the alcohol brands most frequently consumed by underage youth. The present study examines alcohol magazine advertising in 2011 to report age- and sex-specific exposure to advertisements for these brands in contrast with other magazine advertising brands less popular with youth. Method: We licensed magazine advertising occurrence data from Nielsen and magazine audience data from the research company GfK MRI (Growth from Knowledge, Mediamark Research & Intelligence) for national full-run editions for 2011. We contrasted per capita advertising exposure, considering different age- and sex-specific groups, for popular youth brands versus all other magazine brands. For each brand, we reported the age group receiving the highest level of per capita advertising exposure, as well as other age groups within 10% of that peak level. Results: Underage males ages 18–20 were the most heavily exposed age group for 11 of the top 25 brands they consumed and were within 10% of the most heavily exposed group for another 6 brands. Underage females ages 18–20 were most heavily exposed for 16 of the top 25 brands they consumed and were within 10% of the most heavily exposed group for another 2 brands. In contrast, those ages 18–20 were the most heavily exposed group for fewer than 10% of the remaining 308 magazine advertising brands for either sex. Conclusions: These findings suggest a relationship between advertising exposure and youth alcohol brand consumption. Current alcohol industry self-regulatory codes may not be sufficiently protective of youth. PMID:24988260

  7. Prologue: understanding children who have been affected by maltreatment and prenatal alcohol exposure.

    PubMed

    Hyter, Yvette D

    2007-04-01

    This prologue introduces an important topic for multiple disciplines involved with children and their families. This introduction includes a review of some of the current literature on the effects of maltreatment and prenatal alcohol exposure on child development, an explanation of why this topic is essential learning for communication professionals, prevalence figures for the occurrence of these effects, and a summarization of the articles that have been contributed by a cross section of researchers from various disciplines.

  8. Chronic exposure to alcohol alters network activity and morphology of cultured hippocampal neurons.

    PubMed

    Korkotian, Eduard; Botalova, Alena; Odegova, Tatiana; Segal, Menahem

    2015-03-01

    The effects of chronic exposure to moderate concentrations of ethanol were studied in cultured hippocampal neurons. Network activity, assessed by imaging of [Ca(2+)]i variations, was markedly suppressed following 5 days of exposure to 0.25-1% ethanol. The reduced activity was sustained following extensive washout of ethanol, but the activity recovered by blockade of inhibition with bicuculline. This reduction of network activity was associated with a reduction in rates of mEPSCs, but not in a change in inhibitory synaptic activity. Chronic exposure to ethanol caused a significant reduction in the density of mature dendritic spines, without an effect on dendritic length or arborization. These results indicate that chronic exposure to ethanol causes a reduction in excitatory network drive in hippocampal neurons adding another dimension to the chronic effects of alcohol abuse.

  9. Estimates of Ethanol Exposure in Children from Food not Labeled as Alcohol-Containing.

    PubMed

    Gorgus, Eva; Hittinger, Maike; Schrenk, Dieter

    2016-09-01

    Ethanol is widely used in herbal medicines, e.g., for children. Furthermore, alcohol is a constituent of fermented food such as bread or yogurt and "non-fermented" food such as fruit juices. At the same time, exposure to very low levels of ethanol in children is discussed as possibly having adverse effects on psychomotoric functions. Here, we have analyzed alcohol levels in different food products from the German market. It was found that orange, apple and grape juice contain substantial amounts of ethanol (up to 0.77 g/L). Furthermore, certain packed bakery products such as burger rolls or sweet milk rolls contained more than 1.2 g ethanol/100 g. We designed a scenario for average ethanol exposure by a 6-year-old child. Consumption data for the "categories" bananas, bread and bakery products and apple juice were derived from US and German surveys. An average daily exposure of 10.3 mg ethanol/kg body weight (b.w.) was estimated. If a high (acute) consumption level was assumed for one of the "categories," exposure rose to 12.5-23.3 mg/kg b.w. This amount is almost 2-fold (average) or up to 4-fold (high) higher than the lowest exposure from herbal medicines (6 mg/kg b.w.) suggested to require warning hints for the use in children.

  10. Salivary cortisol levels are elevated in the afternoon and at bedtime in children with prenatal alcohol exposure.

    PubMed

    Keiver, Kathy; Bertram, Chris P; Orr, Alison Pritchard; Clarren, Sterling

    2015-02-01

    Prenatal alcohol exposure can cause dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which may underlie some of the behavioral and adaptive problems seen in individuals with Fetal Alcohol Spectrum Disorders (FASD). Infants prenatally exposed to alcohol show altered basal and post-stress cortisol levels, but it is unknown if this persists beyond 2 years of age. It is also unknown if cortisol levels can be normalized through intervention programs. In this study, we investigated the effects of a physical activity program for children with FASD to determine: 1) if HPA dysregulation persists in school-age children with FASD, and 2) the effect of our program on cortisol levels. Twenty six children (ages 6-14 years) with FASD participated in an 8 week motor skill development program. Salivary cortisol levels were measured in 24 children and compared at 4 time points: before, immediately after, 3 months, and 1 year after program completion. Cortisol levels were also compared to 32 control children to evaluate the long-term effects of prenatal alcohol exposure on HPA regulation. For each time point, saliva was collected on each of 2 days at 3 times in the diurnal cycle: awakening, after school, and just before bedtime. Cortisol levels were significantly higher in the afternoon and at bedtime in children with FASD with confirmed prenatal exposure to high levels of alcohol (alcohol exposure rank 4), compared with Control children or children with FASD with exposure to low or unknown levels of alcohol (alcohol exposure rank 3). The program did not significantly affect cortisol levels in children with FASD as a group. These results provide support for long-term effects of prenatal alcohol exposure on the HPA system in humans, which could increase vulnerability to mental health issues and diseases later in life.

  11. Cross-Lagged Associations Between Substance Use-Related Media Exposure and Alcohol Use During Middle School

    PubMed Central

    Tucker, Joan S.; Miles, Jeremy N. V.; D’Amico, Elizabeth J.

    2013-01-01

    Purpose This study examines the reciprocal longitudinal associations between alcohol or other drug (AOD)-related media exposure and alcohol use among middle school students, and explores whether these associations differ by ethnicity or gender. Methods The analytic sample is 7th grade students who were recruited from 16 California middle schools and surveyed in the spring semester of two academic years. Students reported on their background characteristics, exposure to seven types of AOD-related media content (internet videos, social networking sites, movies, television, magazine advertisements, songs, and video games) in the past 3 months, and alcohol use in the past 30 days. Structural equation modeling was used to examine cross-lagged associations between media exposure and alcohol use. Results Greater AOD-related media exposure in 7th grade was significantly associated with a higher probability of alcohol use in 8th grade (p=.02), and alcohol use in 7th grade was marginally associated with greater AOD-related media exposure in 8th grade (p=.07). These cross-lagged associations did not statistically differ by ethnicity (Hispanic vs. non-Hispanic white) or gender. Further, there was no evidence that certain types of media exposure were more strongly associated with alcohol use than others. Conclusions Results from this study suggest that AOD-related media effects and media selectively form a reciprocal, mutually influencing process that may escalate adolescent alcohol use over time. Addressing adolescents’ exposure to AOD-related media content and its effects on behavior, such as through media literacy education, may hold promise for improving the efficacy of alcohol prevention efforts for middle school students. PMID:23770074

  12. Rape-Myth Congruent Beliefs in Women Resulting from Exposure to Violent Pornography: Effects of Alcohol and Sexual Arousal

    ERIC Educational Resources Information Center

    Davis, Kelly Cue; Norris, Jeanette; George, William H.; Martell, Joel; Heiman, Julia R.

    2006-01-01

    Previous research findings indicate that women suffer a variety of detrimental effects from exposure to violent pornography. This study used an experimental paradigm to examine the effects of a moderate alcohol dose and alcohol expectancies on women's acute reactions to a violent pornographic stimulus. A community sample of female social drinkers…

  13. Ebselen prevents early alcohol-induced liver injury in rats.

    PubMed

    Kono, H; Arteel, G E; Rusyn, I; Sies, H; Thurman, R G

    2001-02-15

    Oxidants have been shown to be involved in alcohol-induced liver injury. Moreover, 2-phenyl-1,2-benzisoselenazole-3(2H)-one (ebselen), an organoselenium compound and glutathione peroxidase mimic, decreases oxidative stress and protects against stroke clinically. This study was designed to test the hypothesis that ebselen protects against early alcohol-induced liver injury in rats. Male Wistar rats were fed high-fat liquid diets with or without ethanol (10-16 g/kg/d) continuously for up to 4 weeks using the intragastric enteral feeding protocol developed by Tsukamoto and French. Ebselen (50 mg/kg twice daily, intragastrically) or vehicle (1% tylose) was administered throughout the experiment. Mean urine ethanol concentrations were not significantly different between treatment groups, and ebselen did not affect body weight gains or cyclic patterns of ethanol concentrations in urine. After 4 weeks, serum ALT levels were increased significantly about 4-fold over control values (37 +/- 5 IU/l) by enteral ethanol (112 +/- 7 IU/l); ebselen blunted this increase significantly (61 +/- 8 IU/l). Enteral ethanol also caused severe fatty accumulation, mild inflammation, and necrosis in the liver (pathology score: 4.3 +/- 0.3). In contrast, these pathological changes were blunted significantly by ebselen (pathology score: 2.5 +/- 0.4). While there were no significant effects of either ethanol or ebselen on glutathione peroxidase activity in serum or liver tissue, ebselen blocked the increase in serum nitrate/nitrite caused by ethanol. Furthermore, ethanol increased the activity of NF-kappaB over 5-fold, the number of infiltrating neutrophils 4-fold, and the accumulation of 4-hydroxynonenal over 5-fold. Ebselen blunted all of these effects significantly. These results indicate that ebselen prevents early alcohol-induced liver injury, most likely by preventing oxidative stress, which decreases inflammation.

  14. Distinct neurobehavioral dysfunction based on the timing of developmental binge-like alcohol exposure.

    PubMed

    Sadrian, B; Lopez-Guzman, M; Wilson, D A; Saito, M

    2014-11-07

    Gestational exposure to alcohol can result in long-lasting behavioral deficiencies generally described as fetal alcohol spectrum disorder (FASD). FASD-modeled rodent studies of acute ethanol exposure typically select one developmental window to simulate a specific context equivalent of human embryogenesis, and study consequences of ethanol exposure within that particular developmental epoch. Exposure timing is likely a large determinant in the neurobehavioral consequence of early ethanol exposure, as each brain region is variably susceptible to ethanol cytotoxicity and has unique sensitive periods in their development. We made a parallel comparison of the long-term effects of single-day binge ethanol at either embryonic day 8 (E8) or postnatal day 7 (P7) in male and female mice, and here demonstrate the differential long-term impacts on neuroanatomy, behavior and in vivo electrophysiology of two systems with very different developmental trajectories. The significant long-term differences in odor-evoked activity, local circuit inhibition, and spontaneous coherence between brain regions in the olfacto-hippocampal pathway that were found as a result of developmental ethanol exposure, varied based on insult timing. Long-term effects on cell proliferation and interneuron cell density were also found to vary by insult timing as well as by region. Finally, spatial memory performance and object exploration were affected in P7-exposed mice, but not E8-exposed mice. Our physiology and behavioral results are conceptually coherent with the neuroanatomical data attained from these same mice. Our results recognize both variable and shared effects of ethanol exposure timing on long-term circuit function and their supported behavior.

  15. Chronic postnatal stress induces voluntary alcohol intake and modifies glutamate transporters in adolescent rats.

    PubMed

    Odeon, María Mercedes; Andreu, Marcela; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2015-01-01

    Postnatal stress alters stress responses for life, with serious consequences on the central nervous system (CNS), involving glutamatergic neurotransmission and development of voluntary alcohol intake. Several drugs of abuse, including alcohol and cocaine, alter glutamate transport (GluT). Here, we evaluated effects of chronic postnatal stress (CPS) on alcohol intake and brain glutamate uptake and transporters in male adolescent Wistar rats. For CPS from postnatal day (PD) 7, pups were separated from their mothers and exposed to cold stress (4 °C) for 1 h daily for 20 days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7 days (5-7 rats per group), then killed. CPS: (1) increased voluntary ethanol intake, (2) did not affect body weight gain or produce signs of toxicity with alcohol exposure, (3) increased glutamate uptake by hippocampal synaptosomes in vitro and (4) reduced protein levels (Western measurements) in hippocampus and frontal cortex of glial glutamate transporter-1 (GLT-1) and excitatory amino-acid transporter-3 (EAAT-3) but increased glutamate aspartate transporter (GLAST) levels. We propose that CPS-induced decrements in GLT-1 and EAAT-3 expression levels are opposed by activation of a compensatory mechanism to prevent excitotoxicity. A greater role for GLAST in total glutamate uptake to prevent enlarged extracellular glutamate levels is inferred. Although CPS strongly increased intake of ethanol, this had little impact on effects of CPS on brain glutamate uptake or transporters. However, the impact of early life adverse events on glutamatergic neurotransmission may underlie increased alcohol consumption in adulthood.

  16. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  17. Alcohol

    MedlinePlus

    ... parents and other adults use alcohol socially — having beer or wine with dinner, for example — alcohol seems ... besides just hanging out in someone's basement drinking beer all night. Plan a trip to the movies, ...

  18. Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol

    SciTech Connect

    Kaphalia, Bhupendra S.; Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Wu Hai; Boor, Paul J.; Ansari, G.A. Shakeel

    2010-08-01

    Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH{sup -}) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH{sup -} and hepatic ADH-normal (ADH{sup +}) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2 months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was {approx} 1.5-fold greater in ADH{sup -} vs. ADH{sup +} deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH{sup -} deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis.

  19. Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol.

    PubMed

    Kaphalia, Bhupendra S; Bhopale, Kamlesh K; Kondraganti, Shakuntala; Wu, Hai; Boor, Paul J; Ansari, G A Shakeel

    2010-08-01

    Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH(-)) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH(-) and hepatic ADH-normal (ADH(+)) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was ∼1.5-fold greater in ADH(-) vs. ADH(+) deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH(-) deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis.

  20. Prenatal alcohol exposure delays the development of the cortical barrel field in neonatal rats.

    PubMed

    Margret, Cecilia P; Li, Cheng X; Chappell, Tyson D; Elberger, Andrea J; Matta, Shannon G; Waters, Robert S

    2006-06-01

    In-utero alcohol exposure produces sensorimotor developmental abnormalities that often persist into adulthood. The rodent cortical barrel field associated with the representation of the body surface was used as our model system to examine the effect of prenatal alcohol exposure (PAE) on early somatosensory cortical development. In this study, pregnant female rats were intragastrically gavaged daily with high doses of alcohol (6 gm/kg body weight) throughout the first 20 days of pregnancy. Blood alcohol levels were measured in the pregnant dams on gestational days 13 (G13) and G20. The ethanol treated group (EtOH) was compared to the normal control chowfed (CF) group, nutritionally matched pairfed (PF) group, and cross-foster (XF) group. Cortical barrel development was examined in pups across all treatment groups from G25, corresponding to postnatal day 2 (P2), to G32 corresponding to P9. The EtOH and control group pups were weighed, anesthetized, and perfused. Brains were removed and weighed with, and without cerebellum and olfactory bulbs, and neocortex was removed and weighed. Cortices were then flattened, sectioned tangentially, and stained with a metabolic marker, cytochrome oxidase (CO) to reveal the barrel field. Progression of barrel development was distinguished into three categories: (a) absent, (b) cloudy barrel-like pattern, and (c) well-formed barrels with intervening septae. The major findings are: (1) PAE delayed barrel field development by one or more days, (2) the barrel field first appeared as a cloudy pattern that gave way on subsequent days to an adult-like pattern with clearly demarcated intervening septal regions, (3) the barrel field developed differentially in a lateral-to-medial gradient in both alcohol and control groups, (4) PAE delayed birth by one or more days in 53% of the pups, (5) regardless of whether pups were born on G23 (normal expected birth date for non-alcohol controls) or as in the case for the alcohol-delayed pups born as

  1. Long-term effects of neonatal alcohol exposure on photic reentrainment and phase-shifting responses of the activity rhythm in adult rats.

    PubMed

    Allen, Gregg C; Farnell, Yuhua Z; Maeng, Ji-ung; West, James R; Chen, Wei-Jung A; Earnest, David J

    2005-10-01

    In rats, neonatal alcohol (EtOH) exposure coinciding with the period of rapid brain growth produces structural damage in some brain regions that often persists into adulthood and thus may have long-term consequences in the neural regulation of behavior. Because recent findings indicate that the circadian clock located in the rat suprachiasmatic nucleus is vulnerable to alcohol-induced insults during development, the present study examined the long-term effects of neonatal alcohol exposure on the photic regulation of circadian behavior in adult rats. Rat pups were exposed to alcohol (3.0, 4.5, or 6.0 g x kg(-1) x day(-1)) or isocaloric milk formula on postnatal days 4-9 using artificial-rearing methods. At 2 months of age, animals were housed individually and circadian wheel-running behavior was continuously analyzed to determine the effects of neonatal alcohol treatment on the rate of reentrainment to a 6-h advance in the 12-h light:12-h dark photoperiod and the phase-shifting properties of free-running rhythms in response to discrete light pulses on a background of constant darkness. For all doses, neonatal alcohol exposure had a significant effect in reducing the time for reentrainment such that EtOH-treated rats required four to five fewer days than control animals for stable realignment of the activity rhythm to the shifted light-dark cycle. Coupled with the accelerated rate of reentrainment, the amplitude of light-evoked phase delays at circadian time 14 and advances at circadian time 22 in the 4.5 and 6.0 g x kg(-1) x day(-1) EtOH groups was almost twofold greater than that observed in control animals. The present observations indicate that the mechanisms by which photic signals regulate circadian behavior are permanently altered following alcohol exposure during the period of rapid brain development. These long-term alterations in the photic regulation of circadian rhythms may account, at least partially, for some neurobehavioral consequences of prenatal

  2. Alcohol-induced one-carbon metabolism impairment promotes dysfunction of DNA base excision repair in adult brain.

    PubMed

    Fowler, Anna-Kate; Hewetson, Aveline; Agrawal, Rajiv G; Dagda, Marisela; Dagda, Raul; Moaddel, Ruin; Balbo, Silvia; Sanghvi, Mitesh; Chen, Yukun; Hogue, Ryan J; Bergeson, Susan E; Henderson, George I; Kruman, Inna I

    2012-12-21

    The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr(+/-) mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain.

  3. Alcohol-induced One-carbon Metabolism Impairment Promotes Dysfunction of DNA Base Excision Repair in Adult Brain*

    PubMed Central

    Fowler, Anna-Kate; Hewetson, Aveline; Agrawal, Rajiv G.; Dagda, Marisela; Dagda, Raul; Moaddel, Ruin; Balbo, Silvia; Sanghvi, Mitesh; Chen, Yukun; Hogue, Ryan J.; Bergeson, Susan E.; Henderson, George I.; Kruman, Inna I.

    2012-01-01

    The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr+/− mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain. PMID:23118224

  4. Alcoholism.

    ERIC Educational Resources Information Center

    Caliguri, Joseph P., Ed.

    This extensive annotated bibliography provides a compilation of documents retreived from a computerized search of the ERIC, Social Science Citation Index, and Med-Line databases on the topic of alcoholism. The materials address the following areas of concern: (1) attitudes toward alcohol users and abusers; (2) characteristics of alcoholics and…

  5. Alcohol-Induced Oxidative Stress in the Liver

    PubMed Central

    Arteel, Gavin E.

    2008-01-01

    Summary Oxidative stress is increasingly suspected to contribute to the initiation and progression of many disease, including those caused by alcohol exposure. Two major products of reactive oxygen and nitrogen species formation are 4OH-nonenal and 3-nitrotyrosine protein adducts, both of which can be detected by immunohistochemistry. In the past, immunohistochemical techniques have served largely as qualitative measures of changes. However, coupled with digital capture and analysis of photomicrographs, one can now quantitate treatment-related changes with immunohistochemistry. This chapter summarizes techniques for immunohistochemical detection of these products of reactive oxygen and nitrogen species and subsequent image-analysis. Although the methods described herein are based on liver, these techniques have been employed successfully in most tissue types with minor modifications and are therefore broadly applicable. PMID:18369920

  6. Developmental Alcohol Exposure Impairs Activity-Dependent S-Nitrosylation of NDEL1 for Neuronal Maturation.

    PubMed

    Saito, Atsushi; Taniguchi, Yu; Kim, Sun-Hong; Selvakumar, Balakrishnan; Perez, Gabriel; Ballinger, Michael D; Zhu, Xiaolei; Sabra, James; Jallow, Mariama; Yan, Priscilla; Ito, Koki; Rajendran, Shreenath; Hirotsune, Shinji; Wynshaw-Boris, Anthony; Snyder, Solomon H; Sawa, Akira; Kamiya, Atsushi

    2016-07-01

    Neuronal nitric oxide synthase is involved in diverse signaling cascades that regulate neuronal development and functions via S-Nitrosylation-mediated mechanism or the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway activated by nitric oxide. Although it has been studied extensively in vitro and in invertebrate animals, effects on mammalian brain development and underlying mechanisms remain poorly understood. Here we report that genetic deletion of "Nos1" disrupts dendritic development, whereas pharmacological inhibition of the sGC/cGMP pathway does not alter dendritic growth during cerebral cortex development. Instead, nuclear distribution element-like (NDEL1), a protein that regulates dendritic development, is specifically S-nitrosylated at cysteine 203, thereby accelerating dendritic arborization. This post-translational modification is enhanced by N-methyl-D-aspartate receptor-mediated neuronal activity, the main regulator of dendritic formation. Notably, we found that disruption of S-Nitrosylation of NDEL1 mediates impaired dendritic maturation caused by developmental alcohol exposure, a model of developmental brain abnormalities resulting from maternal alcohol use. These results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure.

  7. White Matter Deficits Mediate Effects of Prenatal Alcohol Exposure on Cognitive Development in Childhood

    PubMed Central

    Fan, Jia; Jacobson, Sandra W.; Taylor, Paul A.; Molteno, Christopher D.; Dodge, Neil C.; Stanton, Mark E.; Jacobson, Joseph L.; Meintjes, Ernesta M.

    2016-01-01

    Fetal alcohol spectrum disorders comprise the spectrum of cognitive, behavioral, and neurological impairments caused by prenatal alcohol exposure (PAE). Diffusion tensor imaging (DTI) was performed on 54 children (age 10.1 ±1.0 years) from the Cape Town Longitudinal Cohort, for whom detailed drinking histories obtained during pregnancy are available: 26 with full fetal alcohol syndrome (FAS) or partial FAS (PFAS), 15 nonsyndromal heavily exposed (HE), and 13 controls. Using voxelwise analyses, children with FAS/PFAS showed significantly lower fractional anisotropy (FA) in four white matter (WM) regions and higher mean diffusivity (MD) in seven; three regions of FA and MD differences (left inferior longitudinal fasciculus (ILF), splenium, and isthmus) overlapped, and the fourth FA cluster was located in the same WM bundle (right ILF) as an MD cluster. HE children showed lower FA and higher MD in a subset of these regions. Significant correlations were observed between three continuous alcohol measures and DTI values at cluster peaks, indicating that WM damage in several regions is dose dependent. Lower FA in the regions of interest was attributable primarily to increased radial diffusivity rather than decreased axonal diffusivity, suggesting poorer axon packing density and/or myelination. Multiple regression models indicated that this cortical WM impairment partially mediated adverse effects of PAE on information processing speed and eyeblink conditioning. PMID:27219850

  8. Establishment of the tree shrew as an alcohol-induced Fatty liver model for the study of alcoholic liver diseases.

    PubMed

    Xing, Huijie; Jia, Kun; He, Jun; Shi, Changzheng; Fang, Meixia; Song, Linliang; Zhang, Pu; Zhao, Yue; Fu, Jiangnan; Li, Shoujun

    2015-01-01

    Currently, the pathogenesis of alcoholic liver diseases (ALDs) is not clear. As a result, there is no effective treatment for ALDs. One limitation is the lack of a suitable animal model for use in studying ALDs. The tree shrew is a lower primate animal, characterized by a high-alcohol diet. This work aimed to establish a fatty liver model using tree shrews and to assess the animals' suitability for the study of ALDs. Tree shrews were treated with alcohol solutions (10% and 20%) for two weeks. Hemophysiology, blood alcohol concentrations (BACs), oxidative stress factors, alcohol metabolic enzymes and hepatic pathology were checked and assayed with an automatic biochemical analyzer, enzyme-linked immunosorbent assay (ELISA), western blot, hematoxylin-eosin (HE) staining and oil red O staining, and magnetic resonance imaging (MRI). Compared with the normal group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total cholesterol (TC), triglyceride (TG), reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly enhanced in alcohol-treated tree shrews. However, the activity of reduced glutathione hormone (GSH) and superoxide dismutase (SOD) declined. Notable changes in alcohol dehydrogenase(ADH1), aldehyde dehydrogenase(ALDH2), CYP2E1, UDP-glucuronosyl transferase 1A1 (UGT1A1) and nuclear factor erythroid-related factor 2 (Nrf2) were observed. HE and oil red O staining showed that hepatocyte swelling, hydropic degeneration, and adipohepatic syndrome occurred in the tree shrews. Alcohol can induce fatty liver-like pathological changes and result in alterations in liver function, oxidative stress factors, alcohol metabolism enzymes and Nrf2. Therefore, the established fatty liver model of tree shrews induced by alcohol should be a promising tool for the study of ALDs.

  9. Rape-myth congruent beliefs in women resulting from exposure to violent pornography: effects of alcohol and sexual arousal.

    PubMed

    Davis, Kelly Cue; Norris, Jeanette; George, William H; Martell, Joel; Heiman, Julia R

    2006-09-01

    Previous research findings indicate that women suffer a variety of detrimental effects from exposure to violent pornography. This study used an experimental paradigm to examine the effects of a moderate alcohol dose and alcohol expectancies on women's acute reactions to a violent pornographic stimulus. A community sample of female social drinkers (N = 134) read an eroticized rape depiction after completing an alcohol administration protocol. As predicted, intoxicated participants were less likely to label the depicted events as rape than their sober counterparts. A path analytic model illustrated that participants' self-reported sexual arousal to the stimulus, as influenced by alcohol consumption and expectancies, resulted in increased rape myth congruent perceptions of the victim and decreased labeling of the incident as rape. Findings suggest that acute alcohol intoxication during violent pornography exposure may ultimately result in women developing more calloused attitudes toward rape and rape victims.

  10. Role of cytokines and chemokines in alcohol-induced tumor promotion

    PubMed Central

    Chen, Danlei; Zhang, Fengyun; Ren, Haifeng; Luo, Jia; Wang, Siying

    2017-01-01

    Excessive chronic alcohol consumption has become a worldwide health problem. The oncogenic effect of chronic alcohol consumption is one of the leading concerns. The mechanisms of alcohol-induced tumorigenesis and tumor progression are largely unknown, although many factors have been implicated in the process. This review discusses the recent progress in this research area with concentration on alcohol-induced dysregulation of cytokines and chemokines. Based on the available evidence, we propose that alcohol promotes tumor progression by the dysregulation of the cytokine/chemokine system. In addition, we discuss specific transcription factors and signaling pathways that are involved in the action of these cytokines/chemokines and the oncogenic effect of alcohol. This review provides novel insight into the mechanisms of alcohol-induced tumor promotion. PMID:28360527

  11. Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats.

    PubMed

    Pavón, Francisco Javier; Marco, Eva María; Vázquez, Mariam; Sánchez, Laura; Rivera, Patricia; Gavito, Ana; Mela, Virginia; Alén, Francisco; Decara, Juan; Suárez, Juan; Giné, Elena; López-Moreno, José Antonio; Chowen, Julie; Rodríguez-de-Fonseca, Fernando; Serrano, Antonia; Viveros, María Paz

    Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS), which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID) procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v) in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif) ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in young adult rats

  12. Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats

    PubMed Central

    Vázquez, Mariam; Sánchez, Laura; Rivera, Patricia; Gavito, Ana; Mela, Virginia; Alén, Francisco; Decara, Juan; Suárez, Juan; Giné, Elena; López-Moreno, José Antonio; Chowen, Julie; Rodríguez-de-Fonseca, Fernando; Serrano, Antonia; Viveros, María Paz

    2016-01-01

    Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS), which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID) procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v) in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif) ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in young adult rats

  13. Adolescents’ exposure to tobacco and alcohol content in YouTube music videos

    PubMed Central

    Murray, Rachael; Lewis, Sarah; Leonardi‐Bee, Jo; Dockrell, Martin; Britton, John

    2015-01-01

    Abstract Aims To quantify tobacco and alcohol content, including branding, in popular contemporary YouTube music videos; and measure adolescent exposure to such content. Design Ten‐second interval content analysis of alcohol, tobacco or electronic cigarette imagery in all UK Top 40 YouTube music videos during a 12‐week period in 2013/14; on‐line national survey of adolescent viewing of the 32 most popular high‐content videos. Setting Great Britain. Participants A total of 2068 adolescents aged 11–18 years who completed an on‐line survey. Measurements Occurrence of alcohol, tobacco and electronic cigarette use, implied use, paraphernalia or branding in music videos and proportions and estimated numbers of adolescents who had watched sampled videos. Findings Alcohol imagery appeared in 45% [95% confidence interval (CI) = 33–51%] of all videos, tobacco in 22% (95% CI = 13–27%) and electronic cigarettes in 2% (95% CI = 0–4%). Alcohol branding appeared in 7% (95% CI = 2–11%) of videos, tobacco branding in 4% (95% CI = 0–7%) and electronic cigarettes in 1% (95% CI = 0–3%). The most frequently observed alcohol, tobacco and electronic cigarette brands were, respectively, Absolut Tune, Marlboro and E‐Lites. At least one of the 32 most popular music videos containing alcohol or tobacco content had been seen by 81% (95% CI = 79%, 83%) of adolescents surveyed, and of these 87% (95% CI = 85%, 89%) had re‐watched at least one video. The average number of videos seen was 7.1 (95% CI = 6.8, 7.4). Girls were more likely to watch and also re‐watch the videos than boys, P < 0.001. Conclusions Popular YouTube music videos watched by a large number of British adolescents, particularly girls, include significant tobacco and alcohol content, including branding. PMID:25516167

  14. Adolescent Alcohol Exposure Alters GABAA Receptor Subunit Expression in Adult Hippocampus

    PubMed Central

    Centanni, Samuel W.; Teppen, Tara; Risher, Mary-Louise; Fleming, Rebekah L.; Moss, Julia L.; Acheson, Shawn K.; Mulholland, Patrick J.; Pandey, Subhash C.; Chandler, L. Judson; Swartzwelder, H. Scott

    2014-01-01

    Background The long-term consequences of adolescent alcohol abuse that persist into adulthood are poorly understood and have not been widely investigated. We have shown that intermittent exposure to alcohol during adolescence decreased the amplitude of GABAA receptor-mediated tonic currents in hippocampal dentate granule cells in adulthood. The aim of the present study was to investigate the enduring effects of chronic intermittent alcohol exposure during adolescence or adulthood on the expression of hippocampal GABAA receptors (GABAARs). Methods We used a previously characterized tissue fractionation method to isolate detergent resistant membranes and soluble fractions, followed by western blots to measure GABAAR protein expression. We also measured mRNA levels of GABAAR subunits using quantitative real-time PCR. Results Although the protein levels of α1-, α4- and δ-GABAAR subunits remained stable between postnatal day (PD) 30 (early adolescence) and PD71 (adulthood), the α5-GABAAR subunit was reduced across that period. In rats that were subjected to adolescent intermittent ethanol (AIE) exposure between PD30–46, there was a significant reduction in the protein levels of the δ-GABAAR, in the absence of any changes in mRNA levels, at 48 hours and 26 days after the last ethanol exposure. Protein levels of the α4-GABAAR subunit were significantly reduced, but mRNA levels were increased, 26 days (but not 48 hours) after the last AIE exposure. Protein levels of α5-GABAAR were not changed by AIE, but mRNA levels were reduced at 48hrs but normalized 26 days after AIE. In contrast to the effects of AIE, chronic intermittent exposure to ethanol during adulthood (CIE) had no effect on expression of any of the GABAAR subunits examined. Conclusions AIE produced both short- and long-term alterations of GABAAR subunits mRNA and protein expression in the hippocampus, whereas CIE produced no long lasting effects on those measures. The observed reduction of protein

  15. Patchouli alcohol dampens lipopolysaccharide induced mastitis in mice.

    PubMed

    Li, Yong-Ping; Yuan, Shi-Fang; Cai, Guo-Hong; Wang, Hui; Wang, Ling; Yu, Lei; Ling, Rui; Yun, Jun

    2014-10-01

    Patchouli alcohol (PA), a tricyclic sesquiterpene isolated from Pogostemonis Herba, has been known to exhibit antioxidant, anti-inflammatory, and other important therapeutic activities. The aim of this study was to investigate the effects of PA on LPS-induced mastitis in vivo and the possible mechanism. The mouse model of mastitis was induced by injection of LPS through the duct of mammary gland. Mice were pretreated with dexamethasone or PA 1 h before and 12 h after induction of LPS. The myeloperoxidase activity and inflammatory cytokines production in mammary tissues were determined. The effects of PA on NF-κB signal pathways were analyzed by Western blotting. The results showed that PA inhibited the LPS-induced TNF-α, IL-6, and IL-1β production in a dose manner. It was also observed that PA attenuated mammary histopathologic changes. Furthermore, Western blot analysis showed that PA could inhibit the phosphorylation of NF-κB and IκB induced by LPS. These results indicate that PA inhibits NF-κB signaling pathways to attenuate inflammatory injury induced by LPS. PA may be a potent therapeutic reagent for the prevention of mastitis.

  16. Potential youth exposure to alcohol advertising on the internet: A study of internet versions of popular television programs

    PubMed Central

    Siegel, Michael; Kurland, Rachel P.; Castrini, Marisa; Morse, Catherine; de Groot, Alexander; Retamozo, Cynthia; Roberts, Sarah P.; Ross, Craig S.; Jernigan, David H.

    2015-01-01

    Background No previous paper has examined alcohol advertising on the internet versions of television programs popular among underage youth. Objectives To assess the volume of alcohol advertising on web sites of television networks which stream television programs popular among youth. Methods Multiple viewers analyzed the product advertising appearing on 12 television programs that are available in full episode format on the internet. During a baseline period of one week, six coders analyzed all 12 programs. For the nine programs that contained alcohol advertising, three underage coders (ages 10, 13, and 18) analyzed the programs to quantify the extent of that advertising over a four-week period. Results Alcohol advertisements are highly prevalent on these programs, with nine of the 12 shows carrying alcohol ads, and six programs averaging at least one alcohol ad per episode. There was no difference in alcohol ad exposure for underage and legal age viewers. Conclusions There is a substantial potential for youth exposure to alcohol advertising on the internet through internet-based versions of television programs. The Federal Trade Commission should require alcohol companies to report the underage youth and adult audiences for internet versions of television programs on which they advertise. PMID:27212891

  17. The clinical utility and specificity of parent report of executive function among children with prenatal alcohol exposure.

    PubMed

    Nguyen, Tanya T; Glass, Leila; Coles, Claire D; Kable, Julie A; May, Philip A; Kalberg, Wendy O; Sowell, Elizabeth R; Jones, Kenneth L; Riley, Edward P; Mattson, Sarah N

    2014-08-01

    Prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) result in behavioral issues related to poor executive function (EF). This overlap may hinder clinical identification of alcohol-exposed children. This study examined the relation between parent and neuropsychological measures of EF and whether parent ratings aid in differential diagnosis. Neuropsychological measures of EF, including the Delis-Kaplan Executive Function System (D-KEFS), were administered to four groups of children (8-16 years): alcohol-exposed with ADHD (AE+, n=80), alcohol-exposed without ADHD (AE-, n=36), non-exposed with ADHD (ADHD, n=93), and controls (CON, n=167). Primary caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF). For parent ratings, multivariate analyses of variance revealed main effects of Exposure and ADHD and an interaction between these factors, with significant differences between all groups on nearly all BRIEF scales. For neuropsychological measures, results indicated main effects of Exposure and ADHD, but no interaction. Discriminant function analysis indicated the BRIEF accurately classifies groups. These findings confirm compounded behavioral, but not neuropsychological, effects in the AE+ group over the other clinical groups. Parent-report was not correlated with neuropsychological performance in the clinical groups and may provide unique information about neurobehavior. Parent-report measures are clinically useful in predicting alcohol exposure regardless of ADHD. Results contribute to a neurobehavioral profile of prenatal alcohol exposure.

  18. Prenatal Alcohol Exposure in Rodents As a Promising Model for the Study of ADHD Molecular Basis

    PubMed Central

    Rojas-Mayorquín, Argelia E.; Padilla-Velarde, Edgar; Ortuño-Sahagún, Daniel

    2016-01-01

    A physiological parallelism, or even a causal effect relationship, can be deducted from the analysis of the main characteristics of the “Alcohol Related Neurodevelopmental Disorders” (ARND), derived from prenatal alcohol exposure (PAE), and the behavioral performance in the Attention-deficit/hyperactivity disorder (ADHD). These two clinically distinct disease entities, exhibits many common features. They affect neurological shared pathways, and also related neurotransmitter systems. We briefly review here these parallelisms, with their common and uncommon characteristics, and with an emphasis in the subjacent molecular mechanisms of the behavioral manifestations, that lead us to propose that PAE in rats can be considered as a suitable model for the study of ADHD. PMID:28018163

  19. Pfeiffer-like syndrome with holoprosencephaly: a newborn with maternal smoking and alcohol exposure.

    PubMed

    Su, Pen-Hua; Chen, Jia-Yuh; Lee, Inn-Chi; Ng, Yan-Yan; Hu, Jui-Ming; Chen, Suh-Jen

    2009-10-01

    We report the case of a female infant with Pfeiffer-like syndrome and holoprosencephaly. She had a cloverleaf skull, ocular proptosis, broad thumbs and halluces, and variable accompanying anomalies compatible with Pfeiffer syndrome. She also displayed microcephaly, short palpebral fissures, and a smooth philtrum, which are clinical signs consistent with fetal alcohol syndrome. She suffered from multiple congenital anomalies and died at 41 days of age. Cardio-pulmonary failure, brain abnormalities, prematurity, and multiple complications contributed to her death. The patient displayed normal chromosomal numbers and type. DNA analysis did not reveal fibrobtast growth factor receptor (FGFR) genes FGFR1, FGFR2, FGFR3 or TWIST gene mutations. We review the previous reports of Pfeiffer syndrome and holoprosencephaly and describe our infant patient with Pfeiffer-like syndrome, holoprosencephaly, and heavy in utero maternal alcohol and smoking exposures.

  20. The effects of prenatal and postnatal (via nursing) exposure to alcohol in rats

    SciTech Connect

    Nekvasil, N.; Baggio, C. )

    1992-02-26

    Pregnant and post-partum rats were given daily doses of 20% alcohol during days 13-21 gestation and postnatal days 3-12, respectively. Following exposure, all rat pups, were tested for balance, blood pressure, right and left cerebral hemisphere weights, and cerebellar weight. Results were grouped according to exposure and gender. The postnatal group was the only one to demonstrate difficulties with balance. The mean arterial pressure in males exposed postnatally was significantly lower than the control and prenatal males. Females exposed postnatally had a significantly higher blood pressure than control females. Within the postnatal group, males had a significantly lower blood pressure than the females. Prenatal and control females differed significantly for left cerebral hemisphere (LCH) weight with the prenatal weighing less. Male pups exposed prenatally had significantly heavier LCH than the postnatal and control males. For both males and females, postnatal LCH weights did not differ from those of the control pups. Within the prenatal group, the LCH weight in females was significantly lower than in males. Mean cerebellar weights were significantly lower in postnatal animals compared to control animals. A major finding of this study is that the effect of alcohol exposure on rat pups depends on gender and developmental age.

  1. Effect of prenatal alcohol exposure on bony craniofacial development: a mouse MicroCT study.

    PubMed

    Shen, Li; Ai, Huisi; Liang, Yun; Ren, Xiaowei; Anthony, Charles Bruce; Goodlett, Charles R; Ward, Richard; Zhou, Feng C

    2013-08-01

    Craniofacial bone dysmorphology is an important but under-explored potential diagnostic feature of fetal alcohol spectrum disorders. This study used longitudinal MicroCT 3D imaging to examine the effect of prenatal alcohol exposure on craniofacial bone growth in a mouse model. C57BL/6J dams were divided into 3 groups: alcohol 4.2% v/v in PMI® liquid diet (ALC), 2 weeks prior to and during pregnancy from embryonic (E) days 7-E16; pair-fed controls (PF), isocalorically matched to the ALC group; chow controls (CHOW), given ad libitum chow and water. The MicroCT scans were performed on pups on postnatal days 7 (P7) and P21. The volumes of the neurocranium (volume encased by the frontal, parietal, and occipital bones) and the viscerocranium (volume encased by the mandible and nasal bone), along with total skull bone volume, head size, and head circumference were evaluated using general linear models and discriminant analyses. The pups in the alcohol-treated group, when compared to the chow-fed controls (ALC vs CHOW) and the isocaloric-fed controls (ALC vs PF), showed differences in head size and circumference at P7 and P21, the total skull volume and parietal bone volume at P7, and volume of all the tested bones except nasal at P21. There was a growth trend of ALC < CHOW and ALC < PF. While covarying for gender and head size or circumference, the treatment affected the total skull and mandible at P7 (ALC > CHOW), and the total skull, parietal bone, and occipital bone at P21 (ALC < CHOW, ALC < PF). While covarying for the P7 measures, the treatment affected only the 3 neurocranial bones at P21 (ALC < CHOW, ALC < PF). Discriminant analysis sensitively selected between ALC and CHOW (AUC = 0.967), between ALC and PF (AUC = 0.995), and between PF and CHOW (AUC = 0.805). These results supported our hypothesis that craniofacial bones might be a reliable and sensitive indicator for the diagnosis of prenatal alcohol exposure. Significantly, we found that the neurocranium (upper

  2. The Effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on Alcohol-Induced Liver Injury

    PubMed Central

    Zhang, Yu-Jie; Zhou, Tong; Wang, Fang; Zhou, Yue; Li, Ya; Zhang, Jiao-Jiao; Zheng, Jie; Xu, Dong-Ping; Li, Hua-Bin

    2016-01-01

    Previous studies have shown that fruits have different effects on alcohol metabolism and alcohol-induced liver injury. The present work selected three fruits and aimed at studying the effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on alcohol-induced liver injury in mice. The animals were treated daily with alcohol and fruit juices for fifteen days. Chronic treatment with alcohol increased the levels of aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL), triglyceride (TG), malondialdehyde (MDA), and decreased total protein (TP). Histopathological evaluation also showed that ethanol induced extensive fat droplets in hepatocyte cytoplasm. Syzygium samarangense and Passiflora edulis normalized various biochemical parameters. Solanum muricatum increased the level of ALT and induced infiltration of inflammatory cells in the liver. These results strongly suggest that treatment with Syzygium samarangense and Passiflora edulis could protect liver from the injury of alcohol, while Solanum muricatum could aggravate the damage. PMID:27681723

  3. Inactivation of hepatocyte nuclear factor-4α mediates alcohol-induced downregulation of intestinal tight junction proteins

    PubMed Central

    Zhong, Wei; Zhao, Yantao; McClain, Craig J.; Kang, Y. James

    2010-01-01

    Chronic alcohol exposure has been shown to increase the gut permeability in the distal intestine, in part, through induction of zinc deficiency. The present study evaluated the molecular mechanisms whereby zinc deficiency mediates alcohol-induced intestinal barrier dysfunction. Examination of zinc finger transcription factors in the gastrointestinal tract of mice revealed a prominent distribution of hepatocyte nuclear factor-4α (HNF-4α). HNF-4α exclusively localizes in the epithelial nuclei and exhibited an increased abundance in mRNA and protein levels in the distal intestine. Chronic alcohol exposure to mice repressed the HNF-4α gene expression in the ileum and reduced the protein level and DNA binding activity of HNF-4α in all of the intestinal segments with the most remarkable changes in the ileum. Chronic alcohol exposure also decreased the mRNA levels of tight junction proteins, particularly in the ileum. Caco-2 cell culture studies were conducted to determine the role of HNF-4α in regulation of the epithelial tight junction and barrier function. Knockdown of HNF-4α in Caco-2 cells decreased the mRNA and protein levels of tight junction proteins in association with disruption of the epithelial barrier. Alcohol treatment inactivated HNF-4α, which was prevented by N-acetyl-cysteine or zinc. The link between zinc and HNF-4α function was confirmed by zinc deprivation, which inhibited HNF-4α DNA binding activity. These results indicate that inactivation of HNF-4α due to oxidative stress and zinc deficiency is likely a novel mechanism contributing to the deleterious effects of alcohol on the tight junctions and the intestinal barrier function. PMID:20576917

  4. Kupffer Cell Activation by Ambient Air Particulate Matter Exposure May Exacerbate Non-alcoholic Fatty Liver Disease

    PubMed Central

    Tan, Hui-Hui; Fiel, M. Isabel; Sun, Qinghua; Guo, Jinsheng; Gordon, Ronald E.; Chen, Lung-Chi; Friedman, Scott L.; Odin, Joseph A.; Allina, Jorge

    2009-01-01

    Due to increased obesity, non-alcoholic fatty liver disease (NAFLD) is now the most prevalent liver disease in the United States. NAFLD is considered a component of metabolic syndrome, a cluster of disorders that also includes diabetes mellitus, dyslipidemia, arteriosclerosis, and hypertension. Exposure to ambient air particulate matter with aerodynamic diameters < 2.5 µm (PM2.5) is a risk factor for arteriosclerosis as well as lung disease, but its effect on NAFLD is unknown. PM2.5 induces pulmonary dysfunction via toll-like receptor activation on alveolar macrophages. Toll-like receptor activation of Kupffer cells, resident hepatic macrophages, and subsequent pro-inflammatory cytokine production have been shown to play a key role in NAFLD progression. We hypothesized that PM2.5 exposure is a significant risk factor for progression of NAFLD. Thus, following exposure of male C57BL/6 mice fed high fat chow to concentrated air particulate matter (CAPs) or filtered air for 6 wk, progression of NAFLD was evaluated by standardized histological assessment of hepatic inflammation and fibrosis. In mice fed high fat chow, the hepatic inflammatory grade (3.00 ± 0.00 vs. 1.50 ± 0.71, p < 0.001) and fibrosis stage (1.00 ± 0.00 vs. 0.60 ± 0.52, p = 0.023) were both significantly higher in mice exposed to CAPs versus filtered air, respectively. Increased numbers of Kupffer cells contained PM in CAPs-exposed mice (2.00 ± 0.94 vs. 0.20 ± 0.42, respectively, p < 0.001). PM exposure increased IL-6 secretion up to seven fold in a dose-dependent manner by isolated wild-type but not TLR4−/− Kupffer cells (p < 0.050). Conclusion: Ambient PM2.5 exposure may be a significant risk factor for NAFLD progression. PMID:19908945

  5. The relationship between exposure to alcohol-related content on Facebook and predictors of alcohol consumption among female emerging adults.

    PubMed

    Miller, Joseph; Prichard, Ivanka; Hutchinson, Amanda; Wilson, Carlene

    2014-12-01

    Consuming an unhealthy level of alcohol is a significant problem for some young women. Potential determinants of excess consumption include perceptions of usual consumption among peers-perceptions of what is "normal." The present study examined whether perceptions of social normative endorsement of drinking, operationalized by measures of perceived alcohol consumption of close friends (proximal norms), the consumption of the "average student" (distal norms), and the extent of alcohol-related content posted by peers on Facebook were related to alcohol-related attitudes and self-reported consumption. Female university students (n=129; Mage=21.48 years, SD=3.00) completed an online questionnaire assessing Facebook use, perceived alcohol-related norms, and self-reported alcohol attitudes and consumption. Perceptions of the consumption of the average female student were a negative predictor of attitudes. Positive alcohol attitudes, extent of own alcohol-related photographic posts on Facebook, average female student alcohol consumption, and report of male close friend consumption predicted self-report of own alcohol consumption. Interestingly, female close friend norms failed to predict consumption, whereas male close friend norms predicted consumption but not attitudes, suggesting the possibility of separate cognitive pathways for alcohol-related attitudes and behavior. This study builds on existing research by casting new light on predictors of alcohol-related attitudes, as well as describing the potential role of social networking sites such as Facebook in the formation of social norms and the modulation of drinking behavior.

  6. Association among work exposure, alcohol intake, smoking and Dupuytren's disease in a large cohort study (GAZEL)

    PubMed Central

    Descatha, Alexis; Carton, Matthieu; Mediouni, Zakia; Dumontier, Christian; Roquelaure, Yves; Goldberg, Marcel; Zins, Marie; Leclerc, Annette

    2014-01-01

    Objectives In view of the debate of factors in Dupuytren’s disease, we aimed to describe its relationship with certain occupational factors, alcohol intake and smoking. Setting The French GAZEL cohort (employees of Electricité de France and Gaz de France). Participants Participants of the cohort who answered a questionnaire in 2012, that is, 13 587 participants (73.7% of the questionnaire sent). In 2007, self-assessed lifetime occupational biomechanical exposure was recorded (carrying loads, manipulating a vibrating tool and climbing stairs), as well as alcohol intake, smoking and diabetes mellitus. Analyses were performed on high alcohol intake, smoking and duration of relevant work exposure, stratified by gender. Primary and secondary outcome measures From a specific question on Dupuytren’s disease assessed in 2012, the outcome measures were self-reported Dupuytren’s disease (yes/no) and disabling Dupuytren’s disease (including surgery). Results A total of 10 017 men and 3570 women, aged 64–73 years, were included; the mean age for men was 68 years and for women was 65 years. Among men, the following were significantly associated with Dupuytren’s disease: age (OR 1.03 (1.00; 1.06)), diabetes (OR 1.31 (1.07; 1.60)), heavy drinking (OR 1.36 (1.10; 1.69)) and over 15 years of manipulating a vibrating tool at work (OR 1.52 (1.15; 2.02)); except for diabetes, the association with these factors was stronger for disabling Dupuytren’s disease (or surgery), with OR 1.07 (1.03; 1.11), 1.71 (1.25; 2.33) and 1.98(1.34; 2.91), respectively, for age, heavy drinking and over 15 years of manipulating a vibrating tool at work. Among the 3570 women included, 160 reported Dupuytren’s disease (4.5%). The number of cases in the group of women was too low to reach conclusions, although the findings seemed similar for age, diabetes and vibration exposure. Conclusions In this large French cohort study, Dupuytren’s disease in men was associated with high

  7. Multigenerational and transgenerational inheritance of drug exposure: The effects of alcohol, opiates, cocaine, marijuana, and nicotine.

    PubMed

    Yohn, Nicole L; Bartolomei, Marisa S; Blendy, Julie A

    2015-07-01

    Familial inheritance of drug abuse is composed of both genetic and environmental factors. Additionally, epigenetic transgenerational inheritance may provide a means by which parental drug use can influence several generations of offspring. Recent evidence suggests that parental drug exposure produces behavioral, biochemical, and neuroanatomical changes in future generations. The focus of this review is to discuss these multigenerational and transgenerational phenotypes in the offspring of animals exposed to drugs of abuse. Specifically, changes found following the administration of alcohol, opioids, cocaine, marijuana, and nicotine will be discussed. In addition, epigenetic modifications to the genome following administration of these drugs will be detailed as well as their potential for transmission to the next generation.

  8. Neurotrophic peptides, ADNF-9 and NAP, prevent alcohol-induced apoptosis at midgestation in fetal brains of C57BL/6 mouse.

    PubMed

    Sari, Youssef; Weedman, Jason M; Nkrumah-Abrokwah, Maxwell

    2013-01-01

    Prenatal alcohol exposure is known to induce fetal brain growth deficits at different embryonic stages. We focused this study on investigating the neuroprotective effects against alcohol-induced apoptosis at midgestation using activity-dependent neurotrophic factor (ADNF)-9, a peptide (SALLRSIPA) derived from activity-dependent neurotrophic factor, and NAP, a peptide (NAPVSIPQ) derived from activity-dependent neuroprotective protein. We used an established fetal alcohol exposure mouse model. On embryonic day 7 (E7), weight-matched pregnant females were assigned to the following groups: (1) ethanol liquid diet (ALC) group with 25 % (4.49 %, v/v) ethanol-derived calories, (2) pair-fed (PF) control group, (3) ALC combined with i.p. injections (1.5 mg/kg) of ADNF-9 (ALC/ADNF-9) group, (4) ALC combined with i.p. injections (1.5 mg/kg) of NAP (ALC/NAP) group, (5) PF liquid diet combined with i.p. injections of ADNF-9 (PF/ADNF-9) group, and (6) PF liquid diet combined with i.p. injections of NAP (PF/NAP) group. On day 15 (E15), fetal brains were collected, weighed, and assayed for TdT-mediated dUTP nick end labeling (TUNEL) staining. ADNF-9 or NAP was administered daily from E7 to E15 alongside PF or ALC liquid diet exposure. Our results show that NAP and ADNF-9 significantly prevented alcohol-induced weight reduction of fetal brains. Apoptosis was determined by TUNEL staining; NAP or ADNF-9 administration alongside alcohol exposure significantly prevented alcohol-induced increase in TUNEL-positive cells in primordium of the cingulate cortex and ganglionic eminence. These findings may pave the path toward potential therapeutics against alcohol intoxication during pregnancy stages.

  9. Effect of repeated alcohol exposure during the third trimester-equivalent on messenger RNA levels for interleukin-1β, chemokine (C-C motif) ligand 2, and interleukin 10 in the developing rat brain after injection of lipopolysaccharide.

    PubMed

    Topper, Lauren A; Valenzuela, C Fernando

    2014-12-01

    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.

  10. Lead-induced catalase activity differentially modulates behaviors induced by short-chain alcohols.

    PubMed

    Correa, M; Pascual, M; Sanchis-Segura, C; Guerri, C; Aragon, C M G

    2005-11-01

    Acute lead administration produces a transient increase in brain catalase activity. This effect of lead has been used to assess the involvement of brain ethanol metabolism, and therefore centrally formed acetaldehyde, in the behavioral actions of ethanol. In mice, catalase is involved in ethanol and methanol metabolism, but not in the metabolism of other alcohols such as 1-propanol or tert-butanol. In the present study, we assessed the specificity of the effects of lead acetate on catalase-mediated metabolism of alcohols, and the ability of lead to modulate the locomotion and loss of the righting reflex (LRR) induced by 4 different short-chain alcohols. Animals were pretreated i.p. with lead acetate (100 mg/kg) or saline, and 7 days later were injected i.p. with ethanol (2.5 or 4.5 g/kg), methanol (2.5 or 6.0 g/kg), 1-propanol (0.5 or 2.5 g/kg) or tert-butanol (0.5 or 2.0 g/kg) for locomotion and LRR, respectively. Locomotion induced by ethanol was significantly potentiated in lead-treated mice, while methanol-induced locomotion was reduced by lead treatment. The loss of righting reflex induced by ethanol was shorter in lead-treated mice, and lead produced the opposite effect in methanol-treated mice. There was no effect of lead on 1-propanol or tert-butanol-induced behaviors. Lead treatment was effective in inducing catalase activity and protein both in liver and brain. These results support the hypothesis that the effects of lead treatment on ethanol-induced behaviors are related to changes in catalase activity, rather than some nonspecific effect that generalizes to all alcohols.

  11. Alcohol Advertising on Boston's Massachusetts Bay Transportation Authority Transit System: An Assessment of Youths' and Adults' Exposure

    PubMed Central

    Nyborn, Justin A.; Wukitsch, Kimberly; Nhean, Siphannay

    2009-01-01

    Objectives. We investigated the frequency with which alcohol advertisements appeared on Massachusetts Bay Transportation Authority (MBTA) transit lines in Boston, MA, and we calculated adult and youths' exposure to the ads. Methods. We measured the nature and extent of alcohol advertisements on 4 Boston transit lines on 2 separate weekdays 1 month apart in June and July of 2008. We calculated weekday ad exposure for all passengers (all ages) and for Boston Public School student passengers (aged 11–18 years). Results. Alcohol ads were viewed an estimated 1 212 960 times across all Boston-area transit passengers during an average weekday, reaching the equivalent of 42.7% of that population. Alcohol ads were viewed an estimated 18 269 times by Boston Public School student transit passengers during an average weekday, reaching the equivalent of 54.1% of that population. Conclusions. Advertisers reached the equivalent of half of all Boston Public School transit passengers aged 11 to 18 years and the equivalent of nearly half of all transit passengers in the Boston area with an alcohol advertisement each day. Because of the high exposure of underage youths to alcohol advertisements, we recommend that the MBTA prohibit alcohol advertising on the Boston transit system. PMID:19890170

  12. Pharmacological evaluation of alcohol withdrawal-induced inhibition of exploratory behaviour and supersensitivity to harmine-induced tremor.

    PubMed

    Meert, T F

    1994-01-01

    Rats given a liquid diet containing 10% (v/v) alcohol consume high quantities of alcohol. Within 8 hr after cessation of the alcohol intake, the animals will show alcohol-withdrawal reactions including a supersensitivity to harmine-induced tremor and an inhibition of exploratory behaviour in a neutral environment. Several drugs can overcome one or more of these alcohol-withdrawal reactions. A reduction of the alcohol withdrawal-induced inhibition of exploration, in terms of both the number of transits into the open field and the time spent in the open field, was obtained with chlordiazepoxide, ritanserin, mianserin and propranolol. Of these four compounds, propranolol and mianserin were also active against the supersensitivity to both 5.00 and 10.00 mg/kg harmine-induced tremor. Chlordiazepoxide and ritanserin were only active against 5.00 mg/kg harmine. Other compounds that reversed the supersensitivity to harmine-induced tremor during alcohol withdrawal included buspirone, fluoxetine, haloperidol, clonidine, flunarizine and baclofen. Very limited effects on both alcohol-withdrawal reactions were observed with ondansetron, nimodipine and MK-801. Risperidone and SCH 23390 were inactive. These results demonstrate that some alcohol withdrawal reactions can be studied in a systematic way and that various pharmacological agents can differentially interact with these alcohol withdrawal reactions.

  13. Comparison of the deleterious effects of binge drinking-like alcohol exposure in adolescent and adult mice.

    PubMed

    Lacaille, Hélène; Duterte-Boucher, Dominique; Liot, Donovan; Vaudry, Hubert; Naassila, Mickael; Vaudry, David

    2015-03-01

    A major cause of alcohol toxicity is the production of reactive oxygen species generated during ethanol metabolism. The aim of this study was to compare the effect of binge drinking-like alcohol exposure on a panel of genes implicated in oxidative mechanisms in adolescent and adult mice. In adolescent animals, alcohol decreased the expression of genes involved in the repair and protection of oxidative DNA damage such as atr, gpx7, or nudt15 and increased the expression of proapoptotic genes such as casp3. In contrast, in the adult brain, genes activated by alcohol were mainly associated with protective mechanisms that prevent cells from oxidative damage. Whatever the age, iterative binge-like episodes provoked the same deleterious effects as those observed after a single binge episode. In adolescent mice, multiple binge ethanol exposure substantially reduced neurogenesis in the dentate gyrus and impaired short-term memory in the novel object and passive avoidance tests. Taken together, our results indicate that alcohol causes deleterious effects in the adolescent brain which are distinct from those observed in adults. These data contribute to explain the greater sensitivity of the adolescent brain to alcohol toxicity. The effects of alcohol exposure were investigated on genes involved in oxidative mechanisms. In adolescent animals, alcohol decreased the expression of genes involved in DNA repair, a potential cause of the observed decrease of neurogenesis. In contrast, in the adult brain, alcohol increased the expression of genes associated with antioxidant mechanisms. Apoptosis was increase in all groups and converged with other biochemical alterations to enhance short-term memory impairment in the adolescent brain. These data contribute to explain the greater sensitivity of the adolescent brain to alcohol toxicity.

  14. Changes in health professionals' knowledge, attitudes and practice following provision of educational resources about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder.

    PubMed

    Payne, Janet; France, Kathryn; Henley, Nadine; D'Antoine, Heather; Bartu, Anne; O'Leary, Colleen; Elliott, Elizabeth; Bower, Carol

    2011-07-01

    We provided health professionals in Western Australia (WA) with educational resources about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder and assessed changes in their knowledge, attitudes and practice concerning fetal alcohol syndrome (FAS) and alcohol consumption in pregnancy. Following our 2002 survey of health professionals in WA, we developed and distributed educational resources to 3348 health professionals in WA in 2007. Six months later we surveyed 1483 of these health professionals. Prevalence rate ratios [PRR] and 95% confidence intervals [CI] were calculated to compare 2007 results with results from the 2002 survey. Of the 1001 responding health professionals, 69.8% had seen the educational resources; of these 77.1% have used them and 48.5% said the resources had assisted them to change their practice or their intention to change their practice. Compared with 2002, there was an increase in the proportion who knew all the essential features of FAS from 11.7% to 15.8% [PRR 1.35; 95% CI 1.09, 1.67] and had diagnosed FAS, from 4.8% to 7.3% [PRR 1.52; 95% CI 1.08, 2.13]. In 2007, 98.1% of health professionals stated they would advise pregnant women to consider not drinking at all or advise them that no alcohol in pregnancy is the safest choice. Health professionals surveyed in 2007 have increased their knowledge, changed their attitudes and practice about FAS, and altered the advice they give to pregnant women about alcohol consumption since our survey in 2002. It is essential that we build on this change and continue to support health professionals' knowledge, attitudes and practice about the prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder. The educational resources for health professionals may be ordered as hard copies and downloaded from the internet http://www.ichr.uwa.edu.au/alcoholandpregnancy.

  15. Ginger-derived nanoparticles protect against alcohol-induced liver damage

    PubMed Central

    Zhuang, Xiaoying; Deng, Zhong-Bin; Mu, Jingyao; Zhang, Lifeng; Yan, Jun; Miller, Donald; Feng, Wenke; McClain, Craig J.; Zhang, Huang-Ge

    2015-01-01

    Daily exposure of humans to nanoparticles from edible plants is inevitable, but significant advances are required to determine whether edible plant nanoparticles are beneficial to our health. Additionally, strategies are needed to elucidate the molecular mechanisms underlying any beneficial effects. Here, as a proof of concept, we used a mouse model to show that orally given nanoparticles isolated from ginger extracts using a sucrose gradient centrifugation procedure resulted in protecting mice against alcohol-induced liver damage. The ginger-derived nanoparticle (GDN)–mediated activation of nuclear factor erythroid 2-related factor 2 (Nrf2) led to the expression of a group of liver detoxifying/antioxidant genes and inhibited the production of reactive oxygen species, which partially contributes to the liver protection. Using lipid knock-out and knock-in strategies, we further identified that shogaol in the GDN plays a role in the induction of Nrf2 in a TLR4/TRIF-dependent manner. Given the critical role of Nrf2 in modulating numerous cellular processes, including hepatocyte homeostasis, drug metabolism, antioxidant defenses, and cell-cycle progression of liver, this finding not only opens up a new avenue for investigating GDN as a means to protect against the development of liver-related diseases such as alcohol-induced liver damage but sheds light on studying the cellular and molecular mechanisms underlying interspecies communication in the liver via edible plant–derived nanoparticles. PMID:26610593

  16. Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement

    PubMed Central

    Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A.

    2014-01-01

    Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2–24 hours post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16–24 hpf) produced retinal defects like those seen with ethanol exposure between 2–24 hpf. Significantly, during an ethanol-sensitive time window (16–24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects. PMID:25541501

  17. Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement.

    PubMed

    Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A

    2015-03-01

    Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2-24 h post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16-24 hpf) produced retinal defects like those seen with ethanol exposure between 2 and 24 hpf. Significantly, during an ethanol-sensitive time window (16-24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects.

  18. Oxidative stress in alcohol-induced rat parotid sialadenosis.

    PubMed

    Campos, Sara Cristina Gonçalves; Moreira, Denise Aparecida Corrêa; Nunes, Terezinha D'Avila e Silva; Colepicolo, Pio; Brigagão, Maísa Ribeiro Pereira Lima

    2005-07-01

    This study evaluated the effect of chronic ethanol consumption on the oxidative status of rat parotid and submandibular glands. To identify the endogenous response to ethanol ingestion, the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined. In addition, the antioxidant alpha-tocopherol was supplied to the animals in order to estimate its action in ethanol-associated glandular damage. The thiobarbituric acid reactive substances (TBARS), and the protein carbonyl (PC) content, both markers of cellular oxidative stress on lipid and protein structures, respectively, were recorded. Animals subjected to alcohol ingestion showed a low body growth rate with concomitant enlargement of absolute and relative parotid wet weight, compared with pair-fed calorie-controlled rats. Parotid glands of ethanol-treated animals showed increased SOD and GPx activity, and alpha-tocopherol was able to reduce their activities to the control levels. TBARS and PC were enhanced after chronic ethanol treatment in rat parotids. Supplemental alpha-tocopherol suppressed the oxidative ethanol-induced damage in lipid without affecting induced protein oxidation. Submandibular glands revealed no alterations in the weight, enzymatic and oxidative parameters tested due to ethanol and/or alpha-tocopherol ingestion. These findings indicate the involvement of oxidative stress in parotid gland sialadenosis due to ethanol consumption and the capability of alpha-tocopherol to halt lipid damage, although this low-molecular antioxidant compound leads to neither increased glandular weight nor protein oxidation in ethanol-induced parotid alterations.

  19. The effects of exercise on adolescent hippocampal neurogenesis in a rat model of binge alcohol exposure during the brain growth spurt.

    PubMed

    Helfer, Jennifer L; Goodlett, Charles R; Greenough, William T; Klintsova, Anna Y

    2009-10-19

    Exposure to alcohol during the brain growth spurt results in impaired cognition and learning in adulthood. This impairment is accompanied by permanent structural changes in the hippocampal formation. Exercise improves performance on hippocampal-dependent learning and memory tasks and increases adult neurogenesis in the rat hippocampal dentate gyrus. The present study examined the effects of wheel running during adolescence on dentate gyrus cell proliferation and neurogenesis after postnatal binge-like alcohol exposure. On postnatal days (PD) 4-9, pups were either intubated with alcohol in a binge-like manner, sham intubated, or reared normally. On PD30-42, all animals were randomly assigned to two adolescent conditions: wheel running or inactive control. Animals were injected with BrdU every day between PD32 and PD42 and perfused on PD42 or PD72. In inactive control animals at both PD42 and PD72, cell proliferation and neurogenesis did not differ between postnatal treatment groups. Wheel running significantly increased the number of BrdU-labeled cells on PD42 in all three postnatal treatments. On PD72, only the normal controls showed significant increases in survival of newly generated cells resulting from the wheel running. These results indicate that adolescent wheel running can induce comparable increases in cell proliferation and neurogenesis in alcohol-exposed and control rats, but the long-term survival of those newly generated cells is impaired relative normal controls. Exercise may provide a means to stimulate neurogenesis, with implications for amelioration of hippocampal-dependent learning impairments associated with alcohol exposure. However, benefits requiring long-lasting survival of the newly generated cells will depend on identifying ways to promote survival.

  20. CYP2E1 potentiates binge alcohol-induced gut leakiness, steatohepatitis, and apoptosis.

    PubMed

    Abdelmegeed, Mohamed A; Banerjee, Atrayee; Jang, Sehwan; Yoo, Seong-Ho; Yun, Jun-Won; Gonzalez, Frank J; Keshavarzian, Ali; Song, Byoung-Joon

    2013-12-01

    Ethanol-inducible cytochrome P450 2E1 (CYP2E1) contributes to increased oxidative stress and steatosis in chronic alcohol-exposure models. However, its role in binge ethanol-induced gut leakiness and hepatic injury is unclear. This study was aimed at investigating the role of CYP2E1 in binge alcohol-induced gut leakiness and the mechanisms of steatohepatitis. Female wild-type (WT) and Cyp2e1-null mice were treated with three doses of binge ethanol (WT-EtOH or Cyp2e1-null-EtOH) (6g/kg oral gavage at 12-h intervals) or dextrose (negative control). Intestinal histology of only WT-EtOH exhibited epithelial alteration and blebbing of lamina propria, and liver histology obtained at 6h after the last ethanol dose showed elevated steatosis with scattered inflammatory foci. These were accompanied by increased levels of serum endotoxin, hepatic enterobacteria, and triglycerides. All these changes, including the intestinal histology and hepatic apoptosis, determined by TUNEL assay, were significantly reversed when WT-EtOH mice were treated with the specific inhibitor of CYP2E1 chlormethiazole and the antioxidant N-acetylcysteine, both of which suppressed oxidative markers including intestinal CYP2E1. WT-EtOH also exhibited elevated amounts of serum TNF-α, hepatic cytokines, CYP2E1, and lipid peroxidation, with decreased levels of mitochondrial superoxide dismutase and suppressed aldehyde dehydrogenase 2 activity. Increased hepatocyte apoptosis with elevated levels of proapoptotic proteins and decreased levels of active (phosphorylated) p-AKT, p-AMPK, and peroxisome proliferator-activated receptor-α, all of which are involved in fat metabolism and inflammation, were observed in WT-EtOH. These changes were significantly attenuated in the corresponding Cyp2e1-null-EtOH mice. These data indicate that both intestinal and hepatic CYP2E1 induced by binge alcohol seems critical in binge alcohol-mediated increased nitroxidative stress, gut leakage, and endotoxemia; altered fat

  1. CYP2E1 potentiates binge alcohol-induced gut leakiness, steatohepatitis and apoptosis

    PubMed Central

    Abdelmegeed, Mohamed A.; Banerjee, Atrayee; Jang, Sehwan; Yoo, Seong-Ho; Yun, Jun-Won; Gonzalez, Frank J.; Keshavarzian, Ali; Song, Byoung-Joon

    2013-01-01

    Ethanol-inducible cytochrome P450 2E1 (CYP2E1) contributes to increased oxidative stress and steatosis in chronic alcohol-exposure models. However, its role in binge ethanol-induced gut leakiness and hepatic injury is unclear. This study was aimed to investigate the role of CYP2E1 in binge alcohol-induced gut leakiness and the mechanisms of steatohepatitis. Female wild-type (WT) and Cyp2e1-null mice were treated with three doses of binge ethanol (WT-EtOH or Cyp2e1-null-EtOH) (6 g/kg oral gavage at 12-h intervals) or dextrose (negative control). Intestinal histology of only WT-EtOH exhibited epithelial alteration and blebbing of lamina propria while liver histology obtained at 6 h after the last ethanol dose showed elevated steatosis with scattered inflammatory foci. These were accompanied by increased levels of serum endotoxin, hepatic enterobacteria and triglycerides. All these changes including the intestinal histology and hepatic apoptosis, determined by TUNEL assay, were significantly reversed when WT-EtOH mice were treated with the specific inhibitor of CYP2E1 chlormethiazole and the antioxidant N-acetyl-cysteine, both of which suppressed the oxidative markers including intestinal CYP2E1. WT-EtOH also exhibited elevated amounts of serum TNF-α, hepatic cytokines, CYP2E1 and lipid peroxidation with decreased levels of mitochondrial superoxide dismutase and suppressed aldehyde dehydrogenase 2 activity. Increased hepatocyte apoptosis with elevated levels of pro-apoptotic proteins and decreased levels of active (phosphorylated) p-AKT, p-AMPK and peroxisome proliferator-activated receptor-alpha (PPAR-α), all of which are involved in fat metabolism and inflammation, were observed in WT-EtOH. These changes were significantly attenuated in the corresponding Cyp2e1-null-EtOH mice. These data indicate that both intestinal and hepatic CYP2E1 induced by binge alcohol seem critical in the binge alcohol-mediated increased nitroxidative stress, gut leakage, endotoxemia, and

  2. Effect of chronic carbon monoxide exposure on experimental alcoholic liver injury in rats

    SciTech Connect

    Nanji, A.A. ); Jui, L.T.; French, S.W. )

    1989-01-01

    Two groups of experimental animals with pair-fed controls were studied to evaluate the effect of chronic carbon monoxide (CO) exposure on progression of experimental alcoholic liver injury. Eight pairs of male Wistar rats were continuously infused liquid diet and ethanol or isocaloric dextrose for four months. Four pairs were also exposed to CO. Liver damage was followed monthly by serum ALT and morphologic assessment of liver biopsy. Serum levels of ALT were significantly higher in the CO-ethanol group compared to other groups. Electron microscopy revealed a greater degree of cell necrosis in the CO exposed group which explained the significantly higher ALT activity in these animals. Both experimental groups had significantly greater liver damage than controls. Carboxyhemoglobin levels were not different in the ethanol-fed and control group. Our results show that chronic CO exposure enhances liver cell necrosis in ethanol-fed rats thereby lending support to the hypothesis that ethanol and hypoxia enhance cellular disruption in the liver which could be important in the pathogenesis of alcoholic liver disease in rats.

  3. Exposure of Children and Adolescents to Alcohol Marketing on Social Media Websites

    PubMed Central

    Winpenny, Eleanor M.; Marteau, Theresa M.; Nolte, Ellen

    2014-01-01

    Aims: In 2011, online marketing became the largest marketing channel in the UK, overtaking television for the first time. This study aimed to describe the exposure of children and young adults to alcohol marketing on social media websites in the UK. Methods: We used commercially available data on the three most used social media websites among young people in the UK, from December 2010 to May 2011. We analysed by age (6–14 years; 15–24 years) and gender the reach (proportion of internet users who used the site in each month) and impressions (number of individual pages viewed on the site in each month) for Facebook, YouTube and Twitter. We further analysed case studies of five alcohol brands to assess the marketer-generated brand content available on Facebook, YouTube and Twitter in February and March 2012. Results: Facebook was the social media site with the highest reach, with an average monthly reach of 89% of males and 91% of females aged 15–24. YouTube had a similar average monthly reach while Twitter had a considerably lower usage in the age groups studied. All five of the alcohol brands studied maintained a Facebook page, Twitter page and YouTube channel, with varying levels of user engagement. Facebook pages could not be accessed by an under-18 user, but in most cases YouTube content and Twitter content could be accessed by those of all ages. Conclusion: The rise in online marketing of alcohol and the high use of social media websites by young people suggests that this is an area requiring further monitoring and regulation. PMID:24293506

  4. Plasma miRNA Profiles in Pregnant Women Predict Infant Outcomes following Prenatal Alcohol Exposure

    PubMed Central

    Balaraman, Sridevi; Schafer, Jordan J.; Tseng, Alexander M.; Wertelecki, Wladimir; Yevtushok, Lyubov; Zymak-Zakutnya, Natalya; Chambers, Christina D.; Miranda, Rajesh C.

    2016-01-01

    Fetal alcohol spectrum disorders (FASD) are difficult to diagnose since many heavily exposed infants, at risk for intellectual disability, do not exhibit craniofacial dysmorphology or growth deficits. Consequently, there is a need for biomarkers that predict disability. In both animal models and human studies, alcohol exposure during pregnancy resulted in significant alterations in circulating microRNAs (miRNAs) in maternal blood. In the current study, we asked if changes in plasma miRNAs in alcohol-exposed pregnant mothers, either alone or in conjunction with other clinical variables, could predict infant outcomes. Sixty-eight pregnant women at two perinatal care clinics in western Ukraine were recruited into the study. Detailed health and alcohol consumption histories, and 2nd and 3rd trimester blood samples were obtained. Birth cohort infants were assessed by a geneticist and classified as unexposed (UE), heavily prenatally exposed and affected (HEa) or heavily exposed but apparently unaffected (HEua). MiRNAs were assessed in plasma samples using qRT-PCR arrays. ANOVA models identified 11 miRNAs that were all significantly elevated in maternal plasma from the HEa group relative to HEua and UE groups. In a random forest analysis classification model, a combination of high variance miRNAs, smoking history and socioeconomic status classified membership in HEa and UE groups, with a misclassification rate of 13%. The RFA model also classified 17% of the HEua group as UE-like, whereas 83% were HEa-like, at least at one stage of pregnancy. Collectively our data indicate that maternal plasma miRNAs predict infant outcomes, and may be useful to classify difficult-to-diagnose FASD subpopulations. PMID:27828986

  5. Objective assessment of ADHD core symptoms in children with heavy prenatal alcohol exposure.

    PubMed

    Infante, M Alejandra; Moore, Eileen M; Nguyen, Tanya T; Fourligas, Nikolaos; Mattson, Sarah N; Riley, Edward P

    2015-09-01

    Attention deficits are often observed in children with prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) is commonly diagnosed in this population. This study used an objective assessment tool to examine differences between alcohol-exposed and non-exposed children on core symptoms of ADHD: inattention, impulsivity, and hyperactivity. Two groups of individuals, aged 7-14years, participated in the study: alcohol-exposed children (AE, n=43), and non-exposed children (CON, n=54). Subjects were evaluated with the Quotient ADHD System, which provides objective data on ADHD core symptoms by combining an infrared motion tracking system and a computerized continuous performance task. Twelve separate ANCOVAs controlling for the effects of age and sex, were conducted on attention and motion variables. Results revealed that in comparison to the CON group, the AE group was significantly (p's<.05) less accurate, made an increased number of omission errors, had longer response latencies, and increased variability in response time. Moreover, the AE group spent less time staying still, and made an increased number of head movements, which traveled a larger distance, covered a greater area, and demonstrated a less complex movement pattern. No significant group differences were observed on the number of commission errors and temporal scaling. Our findings provide further support for the notion that inattention is a core deficit in children prenatally exposed to alcohol. Results from this study are also consistent with parent reports of increased hyperactivity. The Quotient ADHD System may be a useful objective measure of ADHD symptomatology in children with FASD.

  6. Influence of the degree of exposure to lead on relations between alcohol consumption and the biological indices of lead exposure: epidemiological study in a lead acid battery factory.

    PubMed Central

    Cezard, C; Demarquilly, C; Boniface, M; Haguenoer, J M

    1992-01-01

    Alcohol has been shown to interact with lead to influence haem biosynthesis. The aim of this study was to define the dependence of this interaction on the degree of exposure to lead. Exposure to alcohol was estimated by measurement of alcohol concentrations in a sample of urine collected during the morning (AlcUM) (0.82 (SD 4.36) mmol/l) and in a sample collected during the afternoon (AlcUA) (1.15 (SD 3.49) mmol/l). The biological monitoring of exposure to lead included measurements of blood lead (Pb-B) (1.82 (SD 0.72) mumol/l), urinary delta-aminolaevulinic acid (ALAU) (35.33 (SD 28.00) mumol/l; d = 1.015), and erythrocyte zinc-protoporphyrin (ZPP) (112.90 (SD 83.71) nmol/mmol Hb) concentrations. The study of the influence of the degree of occupational exposure to lead on relations between alcohol consumption and effects of the exposure to lead led to the consideration of two different groups--namely, mildly and strongly exposed subjects. In the first group, individual biological susceptibility seemed to play a preponderant part. In the second, the pool of lead present in the body seemed to be sufficiently important to mask the effects of individual susceptibility. PMID:1390270

  7. Histamine H3 receptor antagonist decreases cue-induced alcohol reinstatement in mice.

    PubMed

    Nuutinen, Saara; Mäki, Tiia; Rozov, Stanislav; Bäckström, Pia; Hyytiä, Petri; Piepponen, Petteri; Panula, Pertti

    2016-07-01

    We have earlier found that the histamine H3 receptor (H3R) antagonism diminishes motivational aspects of alcohol reinforcement in mice. Here we studied the role of H3Rs in cue-induced reinstatement of alcohol seeking in C57BL/6J mice using two different H3R antagonists. Systemic administration of H3R antagonists attenuated cue-induced alcohol seeking suggesting that H3R antagonists may reduce alcohol craving. To understand how alcohol affects dopamine and histamine release, a microdialysis study was performed on C57BL/6J mice and the levels of histamine, dopamine and dopamine metabolites were measured in the nucleus accumbens. Alcohol administration was combined with an H3R antagonist pretreatment to reveal whether modulation of H3R affects the effects of alcohol on neurotransmitter release. Alcohol significantly increased the release of dopamine in the nucleus accumbens but did not affect histamine release. Pretreatment with H3R antagonist ciproxifan did not modify the effect of alcohol on dopamine release. However, histamine release was markedly increased with ciproxifan. In conclusion, our findings demonstrate that H3R antagonism attenuates cue-induced reinstatement of alcohol seeking in mice. Alcohol alone does not affect histamine release in the nucleus accumbens but H3R antagonist instead increases histamine release significantly suggesting that the mechanism by which H3R antagonist inhibits alcohol seeking found in the present study and the decreased alcohol reinforcement, reward and consumption found earlier might include alterations in the histaminergic neurotransmission in the nucleus accumbens. These findings imply that selective antagonists of H3Rs could be a therapeutic strategy to prevent relapse and possibly diminish craving to alcohol use. This article is part of the Special Issue entitled 'Histamine Receptors'.

  8. Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice.

    PubMed

    Farook, Justin M; Krazem, Ali; Lewis, Ben; Morrell, Dennis J; Littleton, John M; Barron, Susan

    2008-09-03

    In the present study, we examined the effects of acamprosate for its ability to reduce handling induced convulsions (HICs) during alcohol withdrawal. Diazepam was used as a positive control. Swiss Webster male mice received three daily IP injections of alcohol (2.5 g/kg) or alcohol (2.5 g/kg)+methylpyrazole (4-MP) (9 mg/kg). (4-MP, being an alcohol dehydrogenase inhibitor slows down the breakdown of alcohol. 4-MP in combination with alcohol exhibits a dramatic increase in blood alcohol level compared to alcohol alone). Ten hours following the last alcohol injection, the mice were picked up by the tail and examined for their seizure susceptibility (HICs). Diazepam, a benzodiazepine known to reduce seizures during alcohol withdrawal, significantly reduced these HICs at doses of 0.25, 0.5 and 1 mg/kg (p's<0.001). Acamprosate, an anti-relapse compound used clinically in newly abstinent alcoholics, also reduced these HICs at doses of 100, 200 and 300 mg/kg (p's<0.05). This study supports the use of acamprosate during periods of alcohol withdrawal as well as during abstinence.

  9. Were James Bond’s drinks shaken because of alcohol induced tremor?

    PubMed Central

    Johnson, Graham; Guha, Indra Neil

    2013-01-01

    Objective To quantify James Bond’s consumption of alcohol as detailed in the series of novels by Ian Fleming. Design Retrospective literature review. Setting The study authors’ homes, in a comfy chair. Participants Commander James Bond, 007; Mr Ian Lancaster Fleming. Main outcome measures Weekly alcohol consumption by Commander Bond. Methods All 14 James Bond books were read by two of the authors. Contemporaneous notes were taken detailing every alcoholic drink taken. Predefined alcohol unit levels were used to calculate consumption. Days when Bond was unable to consume alcohol (such as through incarceration) were noted. Results After exclusion of days when Bond was unable to drink, his weekly alcohol consumption was 92 units a week, over four times the recommended amount. His maximum daily consumption was 49.8 units. He had only 12.5 alcohol free days out of 87.5 days on which he was able to drink. Conclusions James Bond’s level of alcohol intake puts him at high risk of multiple alcohol related diseases and an early death. The level of functioning as displayed in the books is inconsistent with the physical, mental, and indeed sexual functioning expected from someone drinking this much alcohol. We advise an immediate referral for further assessment and treatment, a reduction in alcohol consumption to safe levels, and suspect that the famous catchphrase “shaken, not stirred” could be because of alcohol induced tremor affecting his hands. PMID:24336307

  10. Different digital paths to the keg? How exposure to peers' alcohol-related social media content influences drinking among male and female first-year college students.

    PubMed

    Boyle, Sarah C; LaBrie, Joseph W; Froidevaux, Nicole M; Witkovic, Yong D

    2016-06-01

    Despite speculation that peers' alcohol-related content on social media sites (SMS) may influence the alcohol use behaviors of SMS frequenting college students, this relationship has not been investigated longitudinally. The current prospective study assesses the relationship between exposure to peers' alcohol-related SMS content and later-drinking among first-year college students. Among 408 first-year students, total exposure to peers' alcohol-related content on Facebook, Instagram, and Snapchat during the initial 6 weeks of college predicted alcohol consumption 6 months later. The rather robust relationship persisted even after students' and close friends drinking were accounted for, indicating that alcohol references on SMS do not simply reflect alcohol use behaviors that would otherwise be observed in the absence of SMS and be predictive of later alcohol use. Findings also illuminate important gender differences in the degree to which peers' alcohol-related SMS content influenced later drinking behavior as well as psychological mediators of this relationship. Among females, enhancement drinking motives and beliefs about the role of alcohol in the college experience fully mediated the relationship between SMS alcohol exposure and later drinking. Males, however, evidenced a much stronger predictive relationship between SMS alcohol exposure and second semester drinking, with this relationship only partially explained by perceptions of drinking norms, enhancement drinking motives, and beliefs about the role of alcohol in the college experience. Implications of these findings for college drinking prevention efforts and directions for future research are discussed.

  11. Alcohol induced alterations to the human fecal VOC metabolome.

    PubMed

    Couch, Robin D; Dailey, Allyson; Zaidi, Fatima; Navarro, Karl; Forsyth, Christopher B; Mutlu, Ece; Engen, Phillip A; Keshavarzian, Ali

    2015-01-01

    Studies have shown that excessive alcohol consumption impacts the intestinal microbiota composition, causing disruption of homeostasis (dysbiosis). However, this observed change is not indicative of the dysbiotic intestinal microbiota function that could result in the production of injurious and toxic products. Thus, knowledge of the effects of alcohol on the intestinal microbiota function and their metabolites is warranted, in order to better understand the role of the intestinal microbiota in alcohol associated organ failure. Here, we report the results of a differential metabolomic analysis comparing volatile organic compounds (VOC) detected in the stool of alcoholics and non-alcoholic healthy controls. We performed the analysis with fecal samples collected after passage as well as with samples collected directly from the sigmoid lumen. Regardless of the approach to fecal collection, we found a stool VOC metabolomic signature in alcoholics that is different from healthy controls. The most notable metabolite alterations in the alcoholic samples include: (1) an elevation in the oxidative stress biomarker tetradecane; (2) a decrease in five fatty alcohols with anti-oxidant property; (3) a decrease in the short chain fatty acids propionate and isobutyrate, important in maintaining intestinal epithelial cell health and barrier integrity; (4) a decrease in alcohol consumption natural suppressant caryophyllene; (5) a decrease in natural product and hepatic steatosis attenuator camphene; and (6) decreased dimethyl disulfide and dimethyl trisulfide, microbial products of decomposition. Our results showed that intestinal microbiota function is altered in alcoholics which might promote alcohol associated pathologies.

  12. Alcohol Induced Alterations to the Human Fecal VOC Metabolome

    PubMed Central

    Couch, Robin D.; Dailey, Allyson; Zaidi, Fatima; Navarro, Karl; Forsyth, Christopher B.; Mutlu, Ece; Engen, Phillip A.; Keshavarzian, Ali

    2015-01-01

    Studies have shown that excessive alcohol consumption impacts the intestinal microbiota composition, causing disruption of homeostasis (dysbiosis). However, this observed change is not indicative of the dysbiotic intestinal microbiota function that could result in the production of injurious and toxic products. Thus, knowledge of the effects of alcohol on the intestinal microbiota function and their metabolites is warranted, in order to better understand the role of the intestinal microbiota in alcohol associated organ failure. Here, we report the results of a differential metabolomic analysis comparing volatile organic compounds (VOC) detected in the stool of alcoholics and non-alcoholic healthy controls. We performed the analysis with fecal samples collected after passage as well as with samples collected directly from the sigmoid lumen. Regardless of the approach to fecal collection, we found a stool VOC metabolomic signature in alcoholics that is different from healthy controls. The most notable metabolite alterations in the alcoholic samples include: (1) an elevation in the oxidative stress biomarker tetradecane; (2) a decrease in five fatty alcohols with anti-oxidant property; (3) a decrease in the short chain fatty acids propionate and isobutyrate, important in maintaining intestinal epithelial cell health and barrier integrity; (4) a decrease in alcohol consumption natural suppressant caryophyllene; (5) a decrease in natural product and hepatic steatosis attenuator camphene; and (6) decreased dimethyl disulfide and dimethyl trisulfide, microbial products of decomposition. Our results showed that intestinal microbiota function is altered in alcoholics which might promote alcohol associated pathologies. PMID:25751150

  13. Increased liver-specific proteins in circulating extracellular vesicles as potential biomarkers for drug- and alcohol-induced liver injury

    PubMed Central

    Cho, Young-Eun; Im, Eun-Ju; Moon, Pyong-Gon; Mezey, Esteban; Song, Byoung-Joon; Baek, Moon-Chang

    2017-01-01

    Drug- and alcohol-induced liver injury are a leading cause of liver failure and transplantation. Emerging evidence suggests that extracellular vesicles (EVs) are a source of biomarkers because they contain unique proteins reflecting the identity and tissue-specific origin of the EV proteins. This study aimed to determine whether potentially hepatotoxic agents, such as acetaminophen (APAP) and binge alcohol, can increase the amounts of circulating EVs and evaluate liver-specific EV proteins as potential biomarkers for liver injury. The circulating EVs, isolated from plasma of APAP-exposed, ethanol-fed mice, or alcoholic hepatitis patients versus normal control counterparts, were characterized by proteomics and biochemical methods. Liver specific EV proteins were analyzed by immunoblots and ELISA. The amounts of total and liver-specific proteins in circulating EVs from APAP-treated mice significantly increased in a dose- and time-dependent manner. Proteomic analysis of EVs from APAP-exposed mice revealed that the amounts of liver-specific and/or hepatotoxic proteins were increased compared to those of controls. Additionally, the increased protein amounts in EVs following APAP exposure returned to basal levels when mice were treated with N-acetylcysteine or glutathione. Similar results of increased amounts and liver-specific proteins in circulating EVs were also observed in mice exposed to hepatotoxic doses of thioacetamide or d-galactosamine but not by non-hepatotoxic penicillin or myotoxic bupivacaine. Additionally, binge ethanol exposure significantly elevated liver-specific proteins in circulating EVs from mice and alcoholics with alcoholic hepatitis, compared to control counterparts. These results indicate that circulating EVs in drug- and alcohol-mediated hepatic injury contain liver-specific proteins that could serve as specific biomarkers for hepatotoxicity. PMID:28225807

  14. Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring.

    PubMed

    Ceccanti, Mauro; Coccurello, Roberto; Carito, Valentina; Ciafrè, Stefania; Ferraguti, Giampiero; Giacovazzo, Giacomo; Mancinelli, Rosanna; Tirassa, Paola; Chaldakov, George N; Pascale, Esterina; Ceccanti, Marco; Codazzo, Claudia; Fiore, Marco

    2016-07-01

    Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring.

  15. Glycycoumarin ameliorates alcohol-induced hepatotoxicity via activation of Nrf2 and autophagy.

    PubMed

    Song, Xinhua; Yin, Shutao; Huo, Yazhen; Liang, Min; Fan, Lihong; Ye, Min; Hu, Hongbo

    2015-12-01

    Licorice, a traditional Chinese medicine, has been used to treat various diseases, including liver disease, for centuries. However, the chemical basis and biological mechanisms underlying the biological functions of licorice remain elusive. The purpose of the current study was to test the hepatoprotective effect of glycycoumarin (GCM), a representative coumarin in licorice, using animal models of both chronic and acute alcoholic liver injury. C57BL/6J mice were used to evaluate the hepatoprotective effect of GCM on liver injury induced by either chronic or acute ethanol exposure. AML-12 and HepG2 cells were utilized to determine the functional role of Nrf2 in the hepatoprotective effect of GCM and to decipher the mechanisms of GCM-induced Nrf2 activation. We found that treatment with GCM leads to a significant reduction in hepatotoxicity in response to either chronic or acute ethanol exposure. Further mechanistic investigations reveal that activation of Nrf2 via the p38 pathway and induction of autophagy by GCM contribute to its hepatoprotective activity. In addition, we demonstrate that p62 upregulation by a transcriptional mechanism also contributes to Nrf2 activation via a positive feedback loop. Our study has identified GCM as a novel active ingredient that contributes to the hepatoprotective activity of licorice.

  16. Transdermal delivery of cannabidiol attenuates binge alcohol-induced neurodegeneration in a rodent model of an alcohol use disorder.

    PubMed

    Liput, Daniel J; Hammell, Dana C; Stinchcomb, Audra L; Nixon, Kimberly

    2013-10-01

    Excessive alcohol consumption, characteristic of alcohol use disorders, results in neurodegeneration and behavioral and cognitive impairments that are hypothesized to contribute to the chronic and relapsing nature of alcoholism. Therefore, the current study aimed to advance the preclinical development of transdermal delivery of cannabidiol (CBD) for the treatment of alcohol-induced neurodegeneration. In Experiment 1, 1.0%, 2.5% and 5.0% CBD gels were evaluated for neuroprotection. The 5.0% CBD gel resulted in a 48.8% reduction in neurodegeneration in the entorhinal cortex assessed by Fluoro-Jade B (FJB), which trended to statistical significance (p=0.069). Treatment with the 5.0% CBD gel resulted in day 3 CBD plasma concentrations of ~100.0 ng/mL so this level was used as a target concentration for development of an optimized gel formulation. Experiment 2 tested a next generation 2.5% CBD gel formulation, which was compared to CBD administration by intraperitoneal injection (IP; 40.0 mg/kg/day). This experiment found similar magnitudes of neuroprotection following both routes of administration; transdermal CBD decreased FJB+ cells in the entorhinal cortex by 56.1% (p<0.05), while IP CBD resulted in a 50.6% (p<0.05) reduction in FJB+ cells. These results demonstrate the feasibility of using CBD transdermal delivery systems for the treatment of alcohol-induced neurodegeneration.

  17. Alcohol

    MedlinePlus

    ... created when grains, fruits, or vegetables are fermented . Fermentation is a process that uses yeast or bacteria ... change the sugars in the food into alcohol. Fermentation is used to produce many necessary items — everything ...

  18. Alcohol.

    ERIC Educational Resources Information Center

    Schibeci, Renato

    1996-01-01

    Describes the manufacturing of ethanol, the effects of ethanol on the body, the composition of alcoholic drinks, and some properties of ethanol. Presents some classroom experiments using ethanol. (JRH)

  19. Hepatotherapeutic effect of Aloe vera in alcohol-induced hepatic damage.

    PubMed

    Saka, W A; Akhigbe, R E; Ishola, O S; Ashamu, E A; Olayemi, O T; Adeleke, G E

    2011-07-15

    There is a lack of reliable hepatotherapeutic drugs in modern medicine in the management of alcohol/drug-induced liver damage. Aloe vera extract has been used in folklore medicine for its medicinal values. This study evaluates the hepatotherapeutic activity of aqueous extract of Aloe vera gel in rats. Sprague-Dawley rats were divided into three groups; the negative control, positive control and the extract-treated groups. The negative control received only distilled water daily. The positive control received alcohol, while the extract-treated group received aqueous extract of Aloe vera and alcohol. Hepatotoxicity was induced in the positive control and extract-treated rats with alcohol. The hepatotherapeutic effect was evaluated by performing an assay of the serum total bilirubin, alkaline phosphatase, aspartate and alanine transaminases and liver histopathology. Alanine transaminase activities were comparable in all groups. Alcohol treatment alone significantly (p < 0.05) increased total serum bilirubin, alkaline phosphatase and aspartate transaminase activities. Alcohol-induced hepatic dysfunction was abrogated by Aloe vera extract. Histopathological examination revealed that alcohol induced hepatic damage. Aloe vera treatment maintained hepatic architecture similar to that seen in the control. This study shows that aqueous extract of Aloe vera gel is hepatotherapeutic and thus lends credence to the use of the plant in folklore medicine in the management of alcohol-induced hepatic dysfunction.

  20. Increased DNA double-strand break was associated with downregulation of repair and upregulation of apoptotic factors in rat hippocampus after alcohol exposure.

    PubMed

    Suman, Shubhankar; Kumar, Santosh; N'Gouemo, Prosper; Datta, Kamal

    2016-08-01

    Binge drinking is known to cause damage in critical areas of the brain, including the hippocampus, which is important for relational memory and is reported to be sensitive to alcohol toxicity. However, the roles of DNA double-strand break (DSB) and its repair pathways, homologous recombination (HR), and non-homologous end joining (NHEJ) in alcohol-induced hippocampal injury remain to be elucidated. The purpose of this first study was to assess alcohol-induced DNA DSB and the mechanism by which alcohol affects DSB repair pathways in rat hippocampus. Male Sprague-Dawley rats (8-10 weeks old) were put on a 4-day binge ethanol treatment regimen. Control animals were maintained under similar conditions but were given the vehicle without ethanol. All animals were humanely euthanized 24 h after the last dose of ethanol administration and the hippocampi were dissected for immunoblot and immunohistochemistry analysis. Ethanol exposure caused increased 4-hydroxynonenal (4-HNE) staining as well as elevated γH2AX and 53BP1 foci in hippocampal cells. Immunoblot analysis showed decreased Mre11, Rad51, Rad50, and Ku86 as well as increased Bax and p21 in samples from ethanol-treated rats. Additionally, we also observed increased activated caspase3 staining in hippocampal cells 24 h after ethanol withdrawal. Taken together, our data demonstrated that ethanol concurrently induced DNA DSB, downregulated DSB repair pathway proteins, and increased apoptotic factors in hippocampal cells. We believe these findings will provide the impetus for further research on DNA DSB and its repair pathways in relation to alcohol toxicity in brain.

  1. Progressive alcohol-induced sperm alterations leading to spermatogenic arrest, which was reversed after alcohol withdrawal.

    PubMed

    Sermondade, Nathalie; Elloumi, Hanène; Berthaut, Isabelle; Mathieu, Emmanuelle; Delarouzière, Vanina; Ravel, Célia; Mandelbaum, Jacqueline

    2010-03-01

    This is a report of a 6-year follow-up of a male patient's semen parameters during heavy chronic alcohol intoxication and after withdrawal. A slowly progressive negative impact of alcohol could be observed: isolated moderate teratozoospermia was firstly noted followed by oligoasthenoteratospermia. Then a severe worsening resulted in cryptozoospermia and ultimately in azoospermia. At this moment, the histological analysis of a testicular biopsy revealed a maturation arrest of the germinal cells at the pachytene stage with no mature sperm cells. Alcohol withdrawal was then obtained, allowing a very fast and drastic improvement of semen characteristics; strictly normal semen parameters were observed after no more than 3 months. Taking into consideration these data, patients should be questioned about their alcohol intake before assisted reproductive technology and should be informed about this adverse effect. Moreover, this case report emphasizes how quickly benefits can be obtained after withdrawal, even in the case of heavy chronic alcohol intake.

  2. Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model

    PubMed Central

    Tyler, Christina R.; Allan, Andrea M.

    2014-01-01

    Prenatal alcohol exposure can lead to long-lasting changes in functional and genetic programs of the brain, which may underlie behavioral alterations seen in Fetal Alcohol Spectrum Disorder (FASD). Aberrant fetal programming during gestational alcohol exposure is a possible mechanism by which alcohol imparts teratogenic effects on the brain; however, current methods used to investigate the effects of alcohol on development often rely on either direct application of alcohol in vitro or acute high doses in vivo. In this study, we used our established moderate prenatal alcohol exposure (PAE) model, resulting in maternal blood alcohol content of approximately 20 mM, and subsequent ex vivo cell culture to assess expression of genes related to neurogenesis. Proliferating and differentiating neural progenitor cell culture conditions were established from telencephalic tissue derived from embryonic day (E) 15–17 tissue exposed to alcohol via maternal drinking throughout pregnancy. Gene expression analysis on mRNA derived in vitro was performed using a microarray, and quantitative PCR was conducted for genes to validate the microarray. Student's t tests were performed for statistical comparison of each exposure under each culture condition using a 95% confidence interval. Eleven percent of genes on the array had significantly altered mRNA expression in the prenatal alcohol-exposed neural progenitor culture under proliferating conditions. These include reduced expression of Adora2a, Cxcl1, Dlg4, Hes1, Nptx1, and Vegfa and increased expression of Fgf13, Ndn, and Sox3; bioinformatics analysis indicated that these genes are involved in cell growth and proliferation. Decreased levels of Dnmt1 and Dnmt3a were also found under proliferating conditions. Under differentiating conditions, 7.3% of genes had decreased mRNA expression; these include Cdk5rap3, Gdnf, Hey2, Heyl, Pard6b, and Ptn, which are associated with survival and differentiation as indicated by bioinformatics

  3. Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model.

    PubMed

    Tyler, Christina R; Allan, Andrea M

    2014-08-01

    Prenatal alcohol exposure can lead to long-lasting changes in functional and genetic programs of the brain, which may underlie behavioral alterations seen in Fetal Alcohol Spectrum Disorder (FASD). Aberrant fetal programming during gestational alcohol exposure is a possible mechanism by which alcohol imparts teratogenic effects on the brain; however, current methods used to investigate the effects of alcohol on development often rely on either direct application of alcohol in vitro or acute high doses in vivo. In this study, we used our established moderate prenatal alcohol exposure (PAE) model, resulting in maternal blood alcohol content of approximately 20 mM, and subsequent ex vivo cell culture to assess expression of genes related to neurogenesis. Proliferating and differentiating neural progenitor cell culture conditions were established from telencephalic tissue derived from embryonic day (E) 15-17 tissue exposed to alcohol via maternal drinking throughout pregnancy. Gene expression analysis on mRNA derived in vitro was performed using a microarray, and quantitative PCR was conducted for genes to validate the microarray. Student's t tests were performed for statistical comparison of each exposure under each culture condition using a 95% confidence interval. Eleven percent of genes on the array had significantly altered mRNA expression in the prenatal alcohol-exposed neural progenitor culture under proliferating conditions. These include reduced expression of Adora2a, Cxcl1, Dlg4, Hes1, Nptx1, and Vegfa and increased expression of Fgf13, Ndn, and Sox3; bioinformatics analysis indicated that these genes are involved in cell growth and proliferation. Decreased levels of Dnmt1 and Dnmt3a were also found under proliferating conditions. Under differentiating conditions, 7.3% of genes had decreased mRNA expression; these include Cdk5rap3, Gdnf, Hey2, Heyl, Pard6b, and Ptn, which are associated with survival and differentiation as indicated by bioinformatics analysis

  4. MODERATE PRENATAL ALCOHOL EXPOSURE AND SEROTONIN GENOTYPE INTERACT TO ALTER CNS SEROTONIN FUNCTION IN RHESUS MONKEYS OFFSPRING

    PubMed Central

    Schneider, Mary L.; Moore, Colleen F.; Barr, Christina S.; Larson, Julie A.; Kraemer, Gary W.

    2010-01-01

    Background Moderate prenatal alcohol exposure can contribute to neurodevelopmental impairments and disrupt several neurotransmitter systems. We examined the timing of moderate level alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and levels of primary serotonin and dopamine metabolites in cerebrospinal fluid (CSF) in rhesus monkeys. Methods Thirty-two 30-month old rhesus monkeys (Macaca mulatta) from four groups of females were assessed: (1) early alcohol-exposed group (n = 9), in which mothers voluntarily consumed 0.6 g/kg/day alcohol solution on gestational days 0 – 50; (2) middle-to-late gestation alcohol-exposed group (n = 6), mothers consumed 0.6 g/kg/day alcohol solution on gestational days 50 – 135; (3) a continuous-exposure group (n = 8), mothers consumed 0.6 g/kg/day alcohol solution on gestational days 0 – 135; and (4) controls (n = 9), mothers consumed an isocaloric control solution on gestational days 0 – 50, 50 – 135, or 0 – 135. Serotonin transporter promoter region allelic variants (homozygous s/s or heterozygous s/l versus homozygous l/l) were determined. We examined CSF concentrations of the 5-HT and DA metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), respectively, at baseline and 50 hours after separation from cage-mates, when the monkeys were 30 months old. Results Early- and middle-to-late gestation-alcohol exposed monkeys carrying the short allele had lower concentrations of 5-HIAA in CSF relative to other groups. Concentrations of 5-HIAA in CSF were lower for s allele carriers and increased from baseline relative to pre-separation values, while 5-HIAA levels in l/l allele carriers were not affected by separation. Monkeys carrying the short allele had lower basal concentrations of HVA in CSF compared to monkeys homozygous for the long allele. Conclusion Carrying the s allele of the 5-HT transporter increased the probability of reduced 5-HIAA in early- and middle

  5. Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy.

    PubMed

    Yang, Lili; Rozenfeld, Raphael; Wu, Defeng; Devi, Lakshmi A; Zhang, Zhenfeng; Cederbaum, Arthur

    2014-03-01

    Acute alcohol drinking induces steatosis, and effective prevention of steatosis can protect liver from progressive damage caused by alcohol. Increased oxidative stress has been reported as one mechanism underlying alcohol-induced steatosis. We evaluated whether cannabidiol, which has been reported to function as an antioxidant, can protect the liver from alcohol-generated oxidative stress-induced steatosis. Cannabidiol can prevent acute alcohol-induced liver steatosis in mice, possibly by preventing the increase in oxidative stress and the activation of the JNK MAPK pathway. Cannabidiol per se can increase autophagy both in CYP2E1-expressing HepG2 cells and in mouse liver. Importantly, cannabidiol can prevent the decrease in autophagy induced by alcohol. In conclusion, these results show that cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms including attenuation of alcohol-mediated oxidative stress, prevention of JNK MAPK activation, and increasing autophagy.

  6. DNA Methylation in the Medial Prefrontal Cortex Regulates Alcohol-Induced Behavior and Plasticity

    PubMed Central

    Tapocik, Jenica D.; Juergens, Nathan; Pitcairn, Caleb; Borich, Abbey; Schank, Jesse R.; Sun, Hui; Schuebel, Kornel; Zhou, Zhifeng; Yuan, Qiaoping; Vendruscolo, Leandro F.; Goldman, David; Heilig, Markus

    2015-01-01

    Recent studies have suggested an association between alcoholism and DNA methylation, a mechanism that can mediate long-lasting changes in gene transcription. Here, we examined the contribution of DNA methylation to the long-term behavioral and molecular changes induced by a history of alcohol dependence. In search of mechanisms underlying persistent rather than acute dependence-induced neuroadaptations, we studied the role of DNA methylation regulating medial prefrontal cortex (mPFC) gene expression and alcohol-related behaviors in rats 3 weeks into abstinence following alcohol dependence. Postdependent rats showed escalated alcohol intake, which was associated with increased DNA methylation as well as decreased expression of genes encoding synaptic proteins involved in neurotransmitter release in the mPFC. Infusion of the DNA methyltransferase inhibitor RG108 prevented both escalation of alcohol consumption and dependence-induced downregulation of 4 of the 7 transcripts modified in postdependent rats. Specifically, RG108 treatment directly reversed both downregulation of synaptotagmin 2 (Syt2) gene expression and hypermethylation on CpG#5 of its first exon. Lentiviral inhibition of Syt2 expression in the mPFC increased aversion-resistant alcohol drinking, supporting a mechanistic role of Syt2 in compulsive-like behavior. Our findings identified a functional role of DNA methylation in alcohol dependence-like behavioral phenotypes and a candidate gene network that may mediate its effects. Together, these data provide novel evidence for DNA methyltransferases as potential therapeutic targets in alcoholism. PMID:25878287

  7. DNA methylation in the medial prefrontal cortex regulates alcohol-induced behavior and plasticity.

    PubMed

    Barbier, Estelle; Tapocik, Jenica D; Juergens, Nathan; Pitcairn, Caleb; Borich, Abbey; Schank, Jesse R; Sun, Hui; Schuebel, Kornel; Zhou, Zhifeng; Yuan, Qiaoping; Vendruscolo, Leandro F; Goldman, David; Heilig, Markus

    2015-04-15

    Recent studies have suggested an association between alcoholism and DNA methylation, a mechanism that can mediate long-lasting changes in gene transcription. Here, we examined the contribution of DNA methylation to the long-term behavioral and molecular changes induced by a history of alcohol dependence. In search of mechanisms underlying persistent rather than acute dependence-induced neuroadaptations, we studied the role of DNA methylation regulating medial prefrontal cortex (mPFC) gene expression and alcohol-related behaviors in rats 3 weeks into abstinence following alcohol dependence. Postdependent rats showed escalated alcohol intake, which was associated with increased DNA methylation as well as decreased expression of genes encoding synaptic proteins involved in neurotransmitter release in the mPFC. Infusion of the DNA methyltransferase inhibitor RG108 prevented both escalation of alcohol consumption and dependence-induced downregulation of 4 of the 7 transcripts modified in postdependent rats. Specifically, RG108 treatment directly reversed both downregulation of synaptotagmin 2 (Syt2) gene expression and hypermethylation on CpG#5 of its first exon. Lentiviral inhibition of Syt2 expression in the mPFC increased aversion-resistant alcohol drinking, supporting a mechanistic role of Syt2 in compulsive-like behavior. Our findings identified a functional role of DNA methylation in alcohol dependence-like behavioral phenotypes and a candidate gene network that may mediate its effects. Together, these data provide novel evidence for DNA methyltransferases as potential therapeutic targets in alcoholism.

  8. Comparing diagnostic classification of neurobehavioral disorder associated with prenatal alcohol exposure with the Canadian fetal alcohol spectrum disorder guidelines: a cohort study

    PubMed Central

    Sanders, James L.; Breen, Rebecca E. Hudson; Netelenbos, Nicole

    2017-01-01

    Background: Diagnostic criteria have recently been introduced in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), for neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE). The purpose of this study is to assess the classification of this condition using the Canadian fetal alcohol spectrum disorder (FASD) multidisciplinary diagnostic guidelines as the standard of comparison. First, classification of ND-PAE was compared with Canadian FASD diagnoses of fetal alcohol syndrome (FAS), partial FAS and alcohol-related neurodevelopmental disorder. Second, classification of ND-PAE was compared with FAS and pFAS only, a criterion for which includes facial features highly predictive of prenatal alcohol exposure and effects. Methods: Eighty-two patients underwent multidisciplinary clinical evaluations using the Canadian FASD diagnostic guidelines between 2011 and 2015. Two clinicians independently reviewed patient files for evidence of diagnostic criteria for ND-PAE when applying an impairment cut-off level of 2 or more standard deviations below the mean, or clinically significant impairment in the absence of standardized norm-referenced measures. Results: Good interrater reliability was established between clinicians (κ = 0.79). Classifications of ND-PAE and Canadian FASD diagnoses, including alcohol-related neurodevelopmental disorder, were moderately correlated (Cramer V [82] = 0.44, p < 0.01). However, ND-PAE possessed low sensitivity in FASD identification. Further, there was no correlation between ND-PAE and FAS/pFAS classifications (Cramer V [82] = 0.05, p > 0.05). Interpretation: Although there is considerable overlap between both sets of criteria, ND-PAE was less likely to identify patients with FASD. Although the neurobehavioral domains assessed by ND-PAE are supported in research, its diagnostic structure restricts the identification of FASD at the impairment threshold of 2 or more standard deviations. A

  9. THE INFLUENCE OF EXTRINSIC REINFORCEMENT ON CHILDREN WITH HEAVY PRENATAL ALCOHOL EXPOSURE

    PubMed Central

    Graham, Diana M.; Glass, Leila; Mattson, Sarah N.

    2016-01-01

    Background Prenatal alcohol exposure affects inhibitory control and other aspects of attention and executive function. However, the efficacy of extrinsic reinforcement on these behaviors has not been tested. Methods Alcohol-exposed children (AE; n=34), children with ADHD (ADHD; n=23), and controls (CON; n=31) completed a flanker task with four reward conditions (no reward, reward, reward+occasional response cost, equal probability of reward+response cost). Inhibitory control was tested in the no reward conditions using a 3(group) x 2(flanker type) ANCOVA. Response to reinforcement was tested using 3(group) x 4(reward condition) x 4(flanker type) ANCOVA. Response time (RT) and accuracy were tested independently. Results Groups did not differ on demographic variables. The flanker task was successful in taxing interference control, an aspect of executive attention (i.e., responses to incongruent stimuli were slower than to congruent stimuli) and the AE group demonstrated impaired executive control over the other groups. Overall, the AE group had significantly slower response times compared to the CON and ADHD groups, which did not differ. However, reinforcement improved RT in all groups. While occasional response cost had the greatest benefit in the CON group, the type of reinforcement did not differentially affect the AE and ADHD groups. Accuracy across reward conditions did not differ by group, but was dependent on flanker type and reward condition. Conclusions Alcohol-exposed children, but not children with ADHD, had impaired interference control in comparison to controls, supporting a differential neurobehavioral profile in these two groups. Both clinical groups were equally affected by introduction of reinforcement, although the type of reinforcement did not differentially affect performance as it did in the control group, suggesting that reward or response cost could be used interchangeably to result in the same benefit. PMID:26842253

  10. Influence of prenatal exposure to cimetidine and alcohol on selected morphological parameters of sexual differentiation: a preliminary report.

    PubMed

    McGivern, R F

    1987-01-01

    Pregnant rats were administered ethanol, cimetidine or a combination of both drugs from day 14 of gestation until parturition. Ano-genital (AG) distance measured at birth was significantly reduced in males exposed to cimetidine, but not in males or females exposed to alcohol. AG distance in males exposed to both ethanol and cimetidine also was not reduced, indicating a possible protective influence of ethanol against this effect of cimetidine. Birthweights in both sexes were reduced by prenatal ethanol exposure, both alone and with cimetidine exposure. Prenatal cimetidine exposure, both alone and in combination with ethanol significantly reduced seminal vesicle weights of adult males. However, no long-term effects of ethanol or cimetidine were observed on adrenal, testicular or ovarian weights. These results indicate that when fetal alcohol exposure is restricted to the critical prenatal period for hormonal actions on sexual differentiation, testosterone levels are maintained at an adequate level for normal morphological development of the genitalia.

  11. Pharmacological attenuation of chronic alcoholic pancreatitis induced hypersensitivity in rats

    PubMed Central

    McIlwrath, Sabrina L; Westlund, Karin N

    2015-01-01

    AIM: To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices. METHODS: Experimental rats were fed a modified Lieber-DeCarli alcohol (6%) and high-fat (65%) diet (AHF) for 10 wk while control animals received a regular rodent chow diet. Weekly behavioral tests determined mechanical and heat sensitivity. In week 10 a fasting glucose tolerance test was performed, measuring blood glucose levels before and after a 2 g/kg bodyweight intraperitoneal (i.p.) injection of glucose. Post mortem histological analysis was performed by staining pancreas and liver tissue sections with hematoxylin and eosin. Pancreas sections were also stained with Sirius red and fast green to quantify collagen content. Insulin-expressing cells were identified immunohistochemically in separate sections. Tissue staining density was quantified using Image J software. After mechanical and heat sensitivity became stable (weeks 6-10) in the AHF-fed animals, three different drugs were tested for their efficacy in attenuating pancreatitis associated hypersensitivity: a Group II metabotropic glutamate receptor specific agonist (2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate (APDC, 3 mg/kg, ip; Tocris, Bristol, United Kingdom), nociceptin (20, 60, 200 nmol/kg, ip; Tocris), and morphine sulfate (3 mg/kg, μ-opioid receptor agonist; Baxter Healthcare, Deerfield, IL, United States). RESULTS: Histological analysis of pancreas and liver determined that unlike control rats, AHF fed animals had pancreatic fibrosis, acinar and beta cell atrophy, with steatosis in both organs. Fat vacuolization was significantly increased in AHF fed rats (6.4% ± 1.1% in controls vs 23.8% ± 4.2%, P < 0.05). Rats fed the AHF diet had reduced fasting glucose tolerance in week 10 when peak blood glucose levels reached significantly higher concentrations than controls (127.4 ± 9.2 mg/dL in controls vs 161.0 ± 8.6 mg/dL, P < 0.05). This concurred with a 3.5 fold higher

  12. Multigenerational and Transgenerational Inheritance of Drug Exposure: The effects of alcohol, opiates, cocaine, marijuana, and nicotine

    PubMed Central

    Yohn, Nicole L.; Bartolomei, Marisa S.; Blendy, Julie A.

    2015-01-01

    Familial inheritance of drug abuse is composed of both genetic and environmental factors. Additionally, epigenetic transgenerational inheritance may provide a means by which parental drug use can influence several generations of offspring. Recent evidence suggests that parental drug exposure produces behavioral, biochemical, and neuroanatomical changes in future generations. The focus of this review is to discuss these multigenerational and transgenerational phenotypes in the offspring of animals exposed to drugs of abuse. Specifically, changes found following the administration of alcohol, opioids, cocaine, marijuana, and nicotine will be discussed. In addition, epigenetic modifications to the genome following administration of these drugs will be detailed as well as their potential for transmission to the next generation. PMID:25839742

  13. Initial subjective reward: single-exposure conditioned place preference to alcohol in mice

    PubMed Central

    Grisel, Judith E.; Beasley, John B.; Bertram, Emma C.; Decker, Brooke E.; Duan, Chunyu A.; Etuma, Mahder; Hand, Annie; Locklear, Mallory N.; Whitmire, Matthew P.

    2014-01-01

    Most adults consume alcohol with relative impunity, but about 10–20% of users persist (or progress) in their consumption, despite mounting and serious repercussions. Identifying at-risk individuals before neuroadaptative changes associated with chronic use become well ingrained is thus a key step in mitigating and preventing the end stage disease and its devastating impacts. Explaining liability has been impeded, in part, by the absence of animal models for assessing initial sensitivity to the drug's reinforcing properties, an important endophenotype in the trajectory toward excessive drinking. Here we assess the initial rewarding effects of the drug in a novel application of the conditioned place preference paradigm. In contrast to previous studies that have all employed repeated drug administration, we demonstrated a robust preference for a context paired with a single exposure to 1.5 g/kg EtOH in male and female subjects of three strains. This model validates an assay of initial sensitivity to the subjective rewarding effects of alcohol, a widely used drug with multifarious impacts on both brain and society, and provides a new tool for theory-driven endophenotypic pharmacogenetic approaches to understanding and treating addiction. PMID:25408633

  14. Association of arsenic exposure with smoking, alcohol, and caffeine consumption: data from NHANES 2005-2010.

    PubMed

    Jain, Ram B

    2015-03-01

    Association of arsenic exposure with smoking, alcohol, and caffeine consumption was investigated. Data from National Health and Nutrition Examination Survey for the years 2005-2010 were used for this investigation. Urinary levels of total arsenic (UAS) and dimethylarsonic acid (UDMA) were evaluated for children aged 6-12 years and adolescents and adults aged ≥ 12 years. Urinary levels of arsenobetaine (UAB) were evaluated for adolescents and adults only. Regression models were fitted for log transformed values of UAB, UAS, and UDMA. For the models for children, however, gender, race/ethnicity, SES, and fish/shell fish consumption during the last 30 days were the only independent variables that were included in the models. Nonsmokers were found to have higher levels of UAS and UDMA than smokers. Elevated levels of UAB, UAS, and UDMA were associated with higher amounts of daily alcohol consumption. The associations were in the opposite direction for daily caffeine consumption. Females were found to have statistically significantly lower adjusted levels of UDMA than males for those aged ≥ 12 years. Irrespective of age, those with unclassified race/ethnicity had the highest levels of UAB, UAS, and UDMA and non-Hispanic whites had the lowest levels. Adolescents had the higher levels of UAB, UAS, and UDMA than adults. Higher SES was associated with higher levels of UAB, UAS, and UDMA among adolescents and adults. Irrespective of age, fish consumption was associated with higher levels of UAB, UAS, and UDMA.

  15. Effects of postnatal alcohol exposure on hippocampal gene expression and learning in adult mice.

    PubMed

    Lee, Dong Hoon; Moon, Jihye; Ryu, Jinhyun; Jeong, Joo Yeon; Roh, Gu Seob; Kim, Hyun Joon; Cho, Gyeong Jae; Choi, Wan Sung; Kang, Sang Soo

    2016-04-28

    Fetal alcohol syndrome (FAS) is a condition resulting from excessive drinking by pregnant women. Symptoms of FAS include abnormal facial features, stunted growth, intellectual deficits and attentional dysfunction. Many studies have investigated FAS, but its underlying mechanisms remain unknown. This study evaluated the relationship between alcohol exposure during the synaptogenesis period in postnatal mice and subsequent cognitive function in adult mice. We delivered two injections, separated by 2 h, of ethanol (3 g/kg, ethanol/saline, 20% v/v) to ICR mice on postnatal day 7. After 10 weeks, we conducted a behavioral test, sacrificed the animals, harvested brain tissue and analyzed hippocampal gene expression using a microarray. In ethanol-treated mice, there was a reduction in brain size and decreased neuronal cell number in the cortex, and also cognitive impairment. cDNA microarray results indicated that 1,548 genes showed a > 2-fold decrease in expression relative to control, whereas 974 genes showed a > 2-fold increase in expression relative to control. Many of these genes were related to signal transduction, synaptogenesis and cell membrane formation, which are highlighted in our findings.

  16. Alcohol exposure in utero leads to enhanced prepubertal mammary development and alterations in mammary IGF and estradiol systems.

    PubMed

    Polanco, Tiffany A; Crismale-Gann, Catina; Cohick, Wendie S

    2011-08-01

    Exposure to alcohol during fetal development increases susceptibility to mammary cancer in adult rats. This study determined if early changes in mammary morphology and the insulin-like growth factor (IGF)/estradiol axis are involved in the mechanisms that underlie this increased susceptibility. Pregnant Sprague-Dawley rats were fed a liquid diet containing 6.7% ethanol (alcohol), an isocaloric liquid diet (pair-fed), or rat chow ad libitum from days 11 to 21 of gestation. At birth, female pups were cross-fostered to ad libitum-fed control dams. Offspring were euthanized at postnatal days (PND) 20, 40, or 80. Animals were injected with BrdU before euthanasia, then mammary glands, serum, and livers were collected. Mammary glands from animals exposed to alcohol in utero displayed increased epithelial cell proliferation and aromatase expression at PND 20 and 40. Mammary IGF-I mRNA was higher in alcohol-exposed animals relative to controls at PND 20, while mammary IGFBP-5 mRNA was lower in this group at PND 40. Hepatic IGF-I mRNA expression was increased at all time points in alcohol-exposed animals, however, circulating IGF-I levels were not altered. These data indicate that alcohol exposure in utero may advance mammary development via the IGF and estradiol systems, which could contribute to increased susceptibility to mammary cancer later in life.

  17. Alcohol-induced hepatotoxicity: a role for oxygen free radicals.

    PubMed

    Younes, M; Strubelt, O

    1987-01-01

    Perfusion of isolated rat livers with ethanol at a concentration of 2 g/l (%o) resulted in a release of glutamate-pyruvate-transaminase (GPT) and sorbitol dehydrogenase (SDH) into the perfusate as markers of toxicity. Inhibition of alcohol dehydrogenase by 4-methylpyrazole or of aldehyde dehydrogenase by cyanamide totally abolished ethanol hepatotoxicity despite of a severalfold increase in acetaldehyde concentration in the perfusate. Addition of superoxide dismutase or catalase clearly suppressed the ethanol-induced release of GPT and SDH, suggesting that .O2- and H2O2 are involved in this process. Also, chelation of iron ions by means of desferrioxamine displayed a clear inhibitory action, suggesting the involvement of an iron-catalyzed Haber-Weiss-reaction leading to the formation of .OH radicals in the hepatotoxic response to ethanol. Our data suggest that during the metabolism of acetaldehyde primary reactive oxygen species (.O2-, H2O2) are produced which may interact to yield hydroxyl or .OH-like radicals, which possibly represent the hepatotoxic principle of ethanol.

  18. A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity.

    PubMed

    Linderborg, Klas; Salaspuro, Mikko; Väkeväinen, Satu

    2011-09-01

    The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde. Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 μM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight). Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30s both with (215 vs. 128 μmol/l, p<0.05) and without (258 vs. 89 μmol/l, p<0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages. Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure.

  19. Withdrawal from chronic intermittent alcohol exposure increases dendritic spine density in the lateral orbitofrontal cortex of mice.

    PubMed

    McGuier, Natalie S; Padula, Audrey E; Lopez, Marcelo F; Woodward, John J; Mulholland, Patrick J

    2015-02-01

    Alcohol use disorders (AUDs) are associated with functional and morphological changes in subfields of the prefrontal cortex. Clinical and preclinical evidence indicates that the orbitofrontal cortex (OFC) is critical for controlling impulsive behaviors, representing the value of a predicted outcome, and reversing learned associations. Individuals with AUDs often demonstrate deficits in OFC-dependent tasks, and rodent models of alcohol exposure show that OFC-dependent behaviors are impaired by chronic alcohol exposure. To explore the mechanisms that underlie these impairments, we examined dendritic spine density and morphology, and NMDA-type glutamate receptor expression in the lateral OFC of C57BL/6J mice following chronic intermittent ethanol (CIE) exposure. Western blot analysis demonstrated that NMDA receptors were not altered immediately following CIE exposure or after 7 days of withdrawal. Morphological analysis of basal dendrites of layer II/III pyramidal neurons revealed that dendritic spine density was also not affected immediately after CIE exposure. However, the total density of dendritic spines was significantly increased after a 7-day withdrawal from CIE exposure. The effect of withdrawal on spine density was mediated by an increase in the density of long, thin spines with no change in either stubby or mushroom spines. These data suggest that morphological neuroadaptations in lateral OFC neurons develop during alcohol withdrawal and occur in the absence of changes in the expression of NMDA-type glutamate receptors. The enhanced spine density that follows alcohol withdrawal may contribute to the impairments in OFC-dependent behaviors observed in CIE-treated mice.

  20. Exposure of piglet coronary arterial muscle cells to low alcohol results in elevation of intracellular free Ca2+: relevance to fetal alcohol syndrome.

    PubMed

    Altura, M B; Zhang, A; Cheng, T P; Altura, B T

    1996-10-31

    Chronic exposure of cultured piglet neonatal coronary arterial smooth muscle cells to low concentrations of ethanol (46-115 mg/dl) for 7 days resulted in concentration-dependent elevation in intracellular free Ca2+ ions ([Ca2+i); these rises (22-56%) in [Ca2+]i were not reversible upon short-term exposure to normal, Ca2(+)-containing physiological salt solution. These findings help to provide a rational basis for why ethanol can result in the well-known fetal alcohol syndrome, including cardiac defects and in-utero death.

  1. Activation of mGluR2/3 following stress hormone exposure restores sensitivity to alcohol in rats.

    PubMed

    Jaramillo, Anel A; Randall, Patrick A; Frisbee, Suzanne; Fisher, Kristen R; Besheer, Joyce

    2015-09-01

    Sensitivity to the interoceptive effects of alcohol is blunted following a period of exposure to the stress hormone corticosterone (CORT), an effect that is suggested to be related, in part, to glutamatergic neuroadaptations. Group II metabotropic glutamate receptors (subtypes 2 and 3; mGluR2/3) modulate several drug- and alcohol-related behaviors, including the interoceptive (discriminative stimulus) effects of alcohol. Therefore, we sought to determine if manipulation of mGluR2/3 would restore sensitivity to the interoceptive effects of alcohol following CORT exposure. Using a two-lever drug discrimination task, male Long-Evans rats were trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water. First, the effect of mGluR2/3 antagonism on the discriminative stimulus effects of alcohol was determined using LY341495 (0.3-3.0 mg/kg; intraperitoneal [IP]). Next, the effects of mGluR2/3 antagonism and activation were assessed in discrimination-trained animals exposed to CORT (300 μg/mL) in the home cage drinking water or water only, for 7 days. Following CORT exposure, decreased sensitivity to alcohol (1 g/kg) was observed. Pretreatment with the mGluR2/3 agonist LY379268 (1.0-3.0 mg/kg; IP), but not the mGluR2/3 antagonist (0.3-1.0 mg/kg; IP), restored sensitivity to alcohol. Additionally, in water controls, mGluR2/3 antagonism and mGluR2/3 activation disrupted expression of the discriminative stimulus effects of alcohol. Together, these findings suggest that blunted sensitivity to the interoceptive effects of alcohol following an episode of heightened stress hormone levels may be due to adaptations in mGluR2/3-related systems. The ability of mGluR2/3 activation to restore sensitivity to alcohol under these conditions lends further support for the importance of these receptors under stress-related conditions.

  2. Activation of mGluR2/3 following stress hormone exposure restores sensitivity to alcohol in rats

    PubMed Central

    Jaramillo, Anel A.; Randall, Patrick A.; Frisbee, Suzanne; Fisher, Kristen R.; Besheer, Joyce

    2015-01-01

    Sensitivity to the interoceptive effects of alcohol is blunted following a period of exposure to the stress hormone corticosterone (CORT), an effect that is suggested to be related, in part, to glutamatergic neuroadaptations. Group II metabotropic glutamate receptors (subtypes 2 and 3; mGluR2/3) modulate several drug- and alcohol-related behaviors, including the interoceptive (discriminative stimulus) effects of alcohol. Therefore, we sought to determine if manipulation of mGluR2/3 would restore sensitivity to the interoceptive effects of alcohol following CORT exposure. Using a two-lever drug discrimination task, male Long-Evans rats were trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water. First, the effect of mGluR2/3 antagonism on the discriminative stimulus effects of alcohol was determined using LY341495 (0.3–3.0 mg/kg; intraperitoneal [IP]). Next, the effects of mGluR2/3 antagonism and activation were assessed in discrimination-trained animals exposed to CORT (300 μg/mL) in the home cage drinking water or water only, for 7 days. Following CORT exposure, decreased sensitivity to alcohol (1 g/kg) was observed. Pretreatment with the mGluR2/3 agonist LY379268 (1.0–3.0 mg/kg; IP), but not the mGluR2/3 antagonist (0.3–1.0 mg/kg; IP), restored sensitivity to alcohol. Additionally, in Water controls, mGluR2/3 antagonism and mGluR2/3 activation disrupted expression of the discriminative stimulus effects of alcohol. Together, these findings suggest that blunted sensitivity to the interoceptive effects of alcohol following an episode of heightened stress hormone levels may be due to adaptations in mGluR2/3-related systems. The ability of mGluR2/3 activation to restore sensitivity to alcohol under these conditions lends further support for the importance of these receptors under stress-related conditions. PMID:26142564

  3. Protective effect of oligomeric proanthocyanidins against alcohol-induced liver steatosis and injury in mice.

    PubMed

    Wang, Zhiguo; Su, Bo; Fan, Sumei; Fei, Haixia; Zhao, Wei

    2015-03-20

    The long-term consumption of alcohol has been associated with multiple pathologies at all levels, such as alcoholism, chronic pancreatitis, malnutrition, alcoholic liver disease (ALD) and cancer. In the current study, we investigated the protective effect of oligomeric proanthocyanidins (OPC) against alcohol-induced liver steatosis and injury and the possible mechanisms using ethanol-induced chronic liver damage mouse models. The results showed that OPC significantly improved alcohol-induced dyslipidemia and alleviated liver steatosis by reducing levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total triglyceride (TG), total cholesterol (TC), low-density cholesterol (LDL-c) and liver malondialdehyde (MDA), and increasing levels of serum high-density lipoprotein (HDL-c), liver superoxide dismutase (SOD). Further investigation indicated that OPC markedly decreased the expressions of lipid synthesis genes and inflammation genes such as sterol regulatory element-binding protein-1c (Srebp-1c), protein-2 (Srebp2), interleukin IL-1β, IL-6 and TNF-α. Furthermore, AML-12 cells line was used to investigate the possible mechanisms which indicated that OPC might alleviate liver steatosis and damage through AMP-activated protein kinase (AMPK) activation involving oxidative stress. In conclusion, our study demonstrated excellent protective effect of OPC against alcohol-induced liver steatosis and injury, which could a potential drug for the treatment of alcohol-induced liver injury in the future.

  4. The impact of cyanoglycoside rich fraction isolated from Cassava (Manihot esculenta) on alcohol induced oxidative stress.

    PubMed

    Boby, R G; Indira, M

    2003-09-15

    The effects of feeding a cassava (Manihot esculenta) rich diet on alcohol induced peroxidative damages were investigated in male albino rats. Rats were divided into four groups and maintained for 60 days as follows. (1) CONTROL GROUP: cassava free diet, (2) alcohol group: cassava free diet+ethanol (4 g/kg body wt/day), (3) cassava group: cassava diet and (4) alcohol+cassava group: cassava diet+ethanol (4 g/kg body wt/day). Results revealed that alcohol induced significant lipid peroxidation, since the lipid peroxidation products malondialdehyde (MDA), hydroperoxides and conjugated dienes were elevated in the liver. The activities of free radical scavenging enzymes such as superoxide dismutase (SOD), catalase and glutathione reductase were reduced and glutathione content was decreased in the liver. But the co-administration of a cassava rich diet increased the activity of free radical scavenging enzymes and glutathione content. The level of lipid peroxides in the liver was also decreased on co-administration of cassava. But the oxidative damage caused by cassava was potentiated by alcohol administration. These studies suggested that consumption of alcohol along with cassava offered some protection against the alcohol induced oxidative stress. So we isolated the cyanoglycoside rich fraction from cassava and its impact on rats administered alcohol was also investigated. The results revealed that alcohol induced oxidative stress was potentiated by the co-administration of cyanoglycoside rich fraction. These studies suggested that the fiber and antioxidant vitamins present in the cassava may be playing a protective role against the alcohol induced oxidative stress.

  5. Acute alcohol exposure, acidemia or glutamine administration impacts amino acid homeostasis in ovine maternal and fetal plasma.

    PubMed

    Washburn, Shannon E; Sawant, Onkar B; Lunde, Emilie R; Wu, Guoyao; Cudd, Timothy A

    2013-09-01

    Fetal alcohol syndrome (FAS) is a significant problem in human reproductive medicine. Maternal alcohol administration alters maternal amino acid homeostasis and results in acidemia in both mother and fetus, causing fetal growth restriction. We hypothesized that administration of glutamine, which increases renal ammoniagenesis to regulate acid-base balance, may provide an intervention strategy. This hypothesis was tested using sheep as an animal model. On day 115 of gestation, ewes were anesthetized and aseptic surgery was performed to insert catheters into the fetal abdominal aorta as well as the maternal abdominal aorta and vena cava. On day 128 of gestation, ewes received intravenous administration of saline, alcohol [1.75 g/kg body weight (BW)/h], a bolus of 30 mg glutamine/kg BW, alcohol + a bolus of 30 mg glutamine/kg BW, a bolus of 100 mg glutamine/kg BW, alcohol + a bolus of 100 mg glutamine/kg BW, or received CO2 administration to induce acidemia independent of alcohol. Blood samples were obtained simultaneously from the mother and the fetus at times 0 and 60 min (the time of peak blood alcohol concentration) of the study. Administration of alcohol to pregnant ewes led to a reduction in concentrations of glutamine and related amino acids in plasma by 21-30%. An acute administration of glutamine to ewes, concurrent with alcohol administration, improved the profile of most amino acids (including citrulline and arginine) in maternal and fetal plasma. We suggest that glutamine may have a protective effect against alcohol-induced metabolic disorders and FAS in the ovine model.

  6. Acute alcohol exposure, acidemia or glutamine administration impacts amino acid homeostasis in ovine maternal and fetal plasma

    PubMed Central

    Washburn, Shannon E.; Sawant, Onkar B.; Lunde, Emilie R.; Wu, Guoyao; Cudd, Timothy A.

    2013-01-01

    Fetal alcohol syndrome (FAS) is a significant problem in human reproductive medicine. Maternal alcohol administration alters maternal amino acid homeostasis and results in acidemia in both mother and fetus, causing fetal growth restriction. We hypothesized that administration of glutamine, which increases renal ammoniagenesis to regulate acid-base balance, may provide an intervention strategy. This hypothesis was tested using sheep as an animal model. On day 115 of gestation, ewes were anesthetized and aseptic surgery was performed to insert catheters into the fetal abdominal aorta as well as the maternal abdominal aorta and vena cava. On day 128 of gestation, ewes received intravenous administration of saline, alcohol [1.75 g/kg body weight (BW)/h], a bolus of 30 mg glutamine/kg BW, alcohol + a bolus of 30 mg glutamine/kg BW, a bolus of 100 mg glutamine/kg BW, alcohol + a bolus of 100 mg glutamine/kg BW, or received CO2 administration to induce acidemia independent of alcohol. Blood samples were obtained simultaneously from the mother and the fetus at times 0 and 60 min (the time of peak blood alcohol concentration) of the study. Administration of alcohol to pregnant ewes led to a reduction in concentrations of glutamine and related amino acids in plasma by 21–30%. An acute administration of glutamine to ewes, concurrent with alcohol administration, improved the profile of most amino acids (including citrulline and arginine) in maternal and fetal plasma. We suggest that glutamine may have a protective effect against alcohol-induced metabolic disorders and FAS in the ovine model. PMID:23315157

  7. Is Prenatal Alcohol Exposure Related to Inattention and Hyperactivity Symptoms in Children? Disentangling the Effects of Social Adversity

    ERIC Educational Resources Information Center

    Rodriguez, A.; Olsen, J.; Kotimaa, A. J.; Kaakinen, M.; Moilanen, I.; Henriksen, T. B.; Linnet, K. M.; Miettunen, J.; Obel, C.; Taanila, A.; Ebeling, H.; Jarvelin, M. R.

    2009-01-01

    Background: Studies concerning whether exposure to low levels of maternal alcohol consumption during fetal development is related to child inattention and hyperactivity symptoms have shown conflicting results. We examine the contribution of covariates related to social adversity to resolve some inconsistencies in the extant research by conducting…

  8. Behavioral Effects of Pre- and Postnatal Exposure to Smoking, Alcohol, and Caffeine in 5-Month-Old Infants.

    ERIC Educational Resources Information Center

    Dowler, Jeffrey K.; Jacobson, Sandra W.

    This study examined the behavioral effects of prenatal and postnatal exposure to smoking, alcohol, and caffeinated beverages on 5-month-old infants. The sample consisted of 179 Caucasian infants and their mothers. All mothers were 19 years of age or older and had at least a tenth-grade education. Mental and motor portions of the Bayley Scales of…

  9. CHRONIC ALCOHOL NEUROADAPTATION AND STRESS CONTRIBUTE TO SUSCEPTIBILITY FOR ALCOHOL CRAVING AND RELAPSE

    PubMed Central

    BREESE, GEORGE R.; SINHA, RAJITA; HEILIG, MARKUS

    2010-01-01

    Alcoholism is a chronic relapsing disorder. Major characteristics observed in alcoholics during an initial period of alcohol abstinence are altered physiological functions and a negative emotional state. Evidence suggests that a persistent, cumulative adaptation involving a kindling/allostasis-like process occurs during the course of repeated chronic alcohol exposures that is critical for the negative symptoms observed during alcohol withdrawal. Basic studies have provided evidence for specific neurotransmitters within identified brain sites being responsible for the negative emotion induced by the persistent cumulative adaptation following intermittent-alcohol exposures. After an extended period of abstinence, the cumulative alcohol adaptation increases susceptibility to stress- and alcohol cue-induced negative symptoms and alcohol seeking, both of which can facilitate excessive ingestion of alcohol. In the alcoholic, stressful imagery and alcohol cues alter physiological responses, enhance negative emotion, and induce craving. Brain fMRI imaging following stress and alcohol cues has documented neural changes in specific brain regions of alcoholics not observed in social drinkers. Such altered activity in brain of abstinent alcoholics to stress and alcohol cues is consistent with a continuing ethanol adaptation being responsible. Therapies in alcoholics found to block responses to stress and alcohol cues would presumably be potential treatments by which susceptibility for continued alcohol abuse can be reduced. By continuing to define the neurobiological basis of the sustained alcohol adaptation critical for the increased susceptibility of alcoholics to stress and alcohol cues that facilitate craving, a new era is expected to evolve in which the high rate of relapse in alcoholism is minimized. 250 PMID:20951730

  10. Amphetamine sensitization and cross-sensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats

    PubMed Central

    Uban, Kristina A.; Comeau, Wendy L.; Bodnar, Tamara; Yu, Wayne K.; Weinberg, Joanne; Galea, Liisa A. M.

    2014-01-01

    Rationale Individuals with fetal alcohol spectrum disorder (FASD) are at increased risk for substance use disorders (SUD). In typically developing individuals, susceptibility to SUD is associated with alterations in dopamine and hypothalamic-pituitary-adrenal (HPA) systems, and their interactions. Prenatal alcohol exposure (PAE) alters dopamine and HPA systems, yet effects of PAE on dopamine-HPA interactions are unknown. Amphetamine-stress cross-sensitization paradigms were utilized to investigate sensitivity of dopamine and stress (HPA) systems, and their interactions following PAE. Methods Adult Sprague-Dawley offspring from PAE, pair-fed, and ad libitum-fed control groups were assigned to amphetamine-(1–2mg/kg) or saline-treated conditions, with injections every other day for 15 days. 14 days later, all animals received an amphetamine challenge (1mg/kg) and 5 days later, hormones were measured under basal or acute stress conditions. Amphetamine sensitization (augmented locomotion, days 1–29) and cross-sensitization with acute restraint stress (increased stress hormones, day 34) were assessed. Results PAE rats exhibited a lower threshold for amphetamine sensitization compared to controls, suggesting enhanced sensitivity of dopaminergic systems to stimulant-induced changes. Cross-sensitization between amphetamine (dopamine) and stress (HPA hormone) systems was evident in PAE, but not in control rats. PAE males exhibited increased dopamine receptor expression (mPFC) compared to controls. Conclusions PAE alters induction and expression of sensitization/cross-sensitization, as reflected in locomotor, neural, and endocrine changes, in a manner consistent with increased sensitivity of dopamine and stress systems. These results provide insight into possible mechanisms that could underlie increased prevalence of SUD, as well as the impact of widely prescribed stimulant medications among adolescents with FASD. PMID:25420606

  11. Alcohol-induced apoptosis of canine cerebral vascular smooth muscle cells: role of extracellular and intracellular calcium ions.

    PubMed

    Li, Wenyan; Li, Jianfeng; Liu, Weiming; Altura, Bella T; Altura, Burton M

    2004-01-16

    Exposure of canine cerebral vascular smooth muscle cells (VSMCs) to ethanol (10, 25 and 100 mM) for 1, 3 and 5 days induced apoptosis with its typical characteristics of nuclear shrinkage, condensation, and DNA breakage as well as formation of apoptotic bodies observed by fluorescence staining, terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling and comet assays. Such effects of alcohol on cerebral VSMCs were time- and concentration-dependent. The threshold ethanol concentration for induction of the apoptotic process was found to be 10 mM. Extracellular and intracellular Ca2+ chelators, i.e. ethylglycol-bisbeta-aminoethylether-N,N,N'N'-tetraacetic acid (EGTA, 5 mM) and 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid AM (BAPTA, 10(-6) M), respectively, ameliorated greatly the number of cerebral VSMCs which underwent apoptosis. Verapamil, however, failed to inhibit apoptosis of cerebral VSMCs. From these new findings, we suggest that alcohol-induced apoptosis may contribute to alcohol-induced brain-vascular damage and stroke. In addition, our findings point to potential caution for humans who imbibe two or more standard drinks per day or who undergo 'binge drinking'.

  12. Mechanisms of alcohol-induced endoplasmic reticulum stress and organ injuries.

    PubMed

    Ji, Cheng

    2012-01-01

    Alcohol is readily distributed throughout the body in the blood stream and crosses biological membranes, which affect virtually all biological processes inside the cell. Excessive alcohol consumption induces numerous pathological stress responses, part of which is endoplasmic reticulum (ER) stress response. ER stress, a condition under which unfolded/misfolded protein accumulates in the ER, contributes to alcoholic disorders of major organs such as liver, pancreas, heart, and brain. Potential mechanisms that trigger the alcoholic ER stress response are directly or indirectly related to alcohol metabolism, which includes toxic acetaldehyde and homocysteine, oxidative stress, perturbations of calcium or iron homeostasis, alterations of S-adenosylmethionine to S-adenosylhomocysteine ratio, and abnormal epigenetic modifications. Interruption of the ER stress triggers is anticipated to have therapeutic benefits for alcoholic disorders.

  13. Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo.

    PubMed

    Sommansson, Anna; Saudi, Wan Salman Wan; Nylander, Olof; Sjöblom, Markus

    2013-07-01

    Increased intestinal permeability is often associated with epithelial inflammation, leaky gut, or other pathological conditions in the gastrointestinal tract. We recently found that melatonin decreases basal duodenal mucosal permeability, suggesting a mucosal protective mode of action of this agent. The aim of the present study was to elucidate the effects of melatonin on ethanol-, wine-, and HCl-induced changes of duodenal mucosal paracellular permeability and motility. Rats were anesthetized with thiobarbiturate and a ~30-mm segment of the proximal duodenum was perfused in situ. Effects on duodenal mucosal paracellular permeability, assessed by measuring the blood-to-lumen clearance of ⁵¹Cr-EDTA, motility, and morphology, were investigated. Perfusing the duodenal segment with ethanol (10 or 15% alcohol by volume), red wine, or HCl (25-100 mM) induced concentration-dependent increases in paracellular permeability. Luminal ethanol and wine increased, whereas HCl transiently decreased duodenal motility. Administration of melatonin significantly reduced ethanol- and wine-induced increases in permeability by a mechanism abolished by the nicotinic receptor antagonists hexamethonium (iv) or mecamylamine (luminally). Signs of mucosal injury (edema and beginning of desquamation of the epithelium) in response to ethanol exposure were seen only in a few villi, an effect that was histologically not changed by melatonin. Melatonin did not affect HCl-induced increases in mucosal permeability or decreases in motility. Our results show that melatonin reduces ethanol- and wine-induced increases in duodenal paracellular permeability partly via an enteric inhibitory nicotinic-receptor dependent neural pathway. In addition, melatonin inhibits ethanol-induced increases in duodenal motor activity. These results suggest that melatonin may serve important gastrointestinal barrier functions.

  14. Effects of intermittent binge alcohol exposure on long-term motor function in young rats.

    PubMed

    Forbes, Ashley; Cooze, Jared; Malone, Craig; French, Vanessa; Weber, John T

    2013-03-01

    Ethanol has well described acute effects on motor function, and chronic alcoholism can damage the cerebellum, which is associated with motor coordination, as well as motor learning. Binge drinking is common among preadolescents and adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we analyzed the effects of periadolsecent/adolescent ethanol exposure on motor function in both male and female Sprague-Dawley rats. To simulate binge drinking, animals received an intraperitoneal injection of 25% (v/v) ethanol (3 g/kg) on postnatal days (PND) 25, 26, 29, 30, 33, 34, 37 and 38. On PND 42 and PND 61 animals were tested on their ability to traverse both square and round beams. There were no significant differences in the time to traverse the beams, or the amount of foot slips, between treated and untreated animals. On PND 48 and PND 62, animals were tested using a horizontal ladder walking apparatus. On PND 48 there were no differences in the ability of treated and untreated animals to traverse the ladder. On PND 62, there were no differences in the time to traverse the ladder, but ethanol treated animals had more foot slips than controls. On PND 43, we conducted footprint analysis of control and treated animals, which included measurements of stride length, paw overlap, and angle of foot placement. There was a significant difference in the angle of foot placement between treated and control animals, and this finding was significant for both male and female animals. There was also a significant overall difference in paw overlap between treatment groups. Although this effect was manifested in male animals there was no significant difference in females. These findings suggest that adolescent ethanol exposure can produce long-lasting effects on motor coordination, and that overall, effects are similar in males and females. In a second set of experiments, male rats received i.p. ethanol (3 g/kg) for 7 days (P31

  15. Neuropeptide Y (NPY) -induced reductions in alcohol intake during continuous access and following alcohol deprivation are not altered by restraint stress in alcohol-preferring (P) rats

    PubMed Central

    Bertholomey, Megan L.; Henderson, Angela N.; Badia-Elder, Nancy E.; Stewart, Robert B.

    2010-01-01

    Administration of neuropeptide Y (NPY) reduces anxiety-like behavior and alcohol intake in alcohol-preferring rats. The present experiment examined whether the effects of NPY on alcohol drinking are modulated by stress exposure during continuous access or following ethanol deprivation. Female P rats underwent 6 weeks of continuous access to 15% v/v ethanol and water prior to intracerebroventricular (ICV) cannula implantation. Deprived rats underwent two cycles of 5 days of ethanol exposure followed by 2 days of ethanol deprivation, while non-deprived rats had uninterrupted access to ethanol. Stressed rats in both ethanol access groups were exposed to restraint stress for 1 hour 4-6 hours after ethanol was removed from the deprived group in both cycles. ICV infusions of 5.0 μg NPY or aCSF were administered 48 hours following the deprivation/stress procedure, after which ethanol was returned. Rats showed increased ethanol intake following ethanol deprivation compared to non-deprived controls. Food and water intake were increased, while ethanol intake was decreased, in rats infused with NPY. Stress did not increase ethanol intake or alter the response to NPY. Although no stress effects were found, the present experiment replicates previous findings regarding the effectiveness of NPY in reducing ethanol consumption. Future studies aimed at determining the extent to which stress may affect relapse to ethanol drinking and response to NPY would benefit from implementing different stress paradigms and varying the pattern of ethanol access. PMID:20937300

  16. Cadmium exposure induces hematuria in Korean adults

    SciTech Connect

    Han, Seung Seok; Kim, Myounghee; Lee, Su Mi; Lee, Jung Pyo; Kim, Sejoong; Joo, Kwon Wook; Lim, Chun Soo; Kim, Yon Su; Kim, Dong Ki

    2013-07-15

    Introduction: Toxic heavy metals have adverse effects on human health. However, the risk of hematuria caused by heavy metal exposure has not been evaluated. Methods: Data from 4701 Korean adults were obtained in the Korean National Health and Nutritional Examination Survey (2008–2010). Blood levels of the toxic heavy metals cadmium, lead, and mercury were measured. Hematuria was defined as a result of ≥+1 on a urine dipstick test. The odds ratios (ORs) for hematuria were measured according to the blood heavy metal levels after adjusting for multiple variables. Results: Individuals with blood cadmium levels in the 3rd and 4th quartiles had a greater OR for hematuria than those in the 1st quartile group: 3rd quartile, 1.35 (1.019–1.777; P=0.037); 4th quartile, 1.52 (1.140–2.017; P=0.004). When blood cadmium was considered as a log-transformed continuous variable, the correlation between blood cadmium and hematuria was significant: OR, 1.97 (1.224–3.160; P{sub trend}=0.005). In contrast, no significant correlations between hematuria and blood lead or mercury were found in the multivariate analyses. Discussion: The present study shows that high cadmium exposure is associated with a risk of hematuria. -- Highlights: • A high level of blood cadmium is associated with a high risk of hematuria. • This correlation is independent of several confounding factors. • Blood levels of lead and mercury are not associated with risk of hematuria. • This is the first study on the correlation between cadmium exposure and hematuria risk.

  17. Acetaldehyde reinforcement and motor reactivity in newborns with or without a prenatal history of alcohol exposure

    PubMed Central

    March, Samanta M.; Culleré, Marcela E.; Abate, Paula; Hernández, José I.; Spear, Norman E.; Molina, Juan C.

    2013-01-01

    Animal models have shown that early ontogeny seems to be a period of enhanced affinity to ethanol. Interestingly, the catalase system that transforms ethanol (EtOH) into acetaldehyde (ACD) in the brain, is more active in the perinatal rat compared to adults. ACD has been found to share EtOH's behavioral effects. The general purpose of the present study was to assess ACD motivational and motor effects in newborn rats as a function of prenatal exposure to EtOH. Experiment 1 evaluated if ACD (0.35 μmol) or EtOH (0.02 μmol) supported appetitive conditioning in newborn pups prenatally exposed to EtOH. Experiment 2 tested if prenatal alcohol exposure modulated neonatal susceptibility to ACD's motor effects (ACD dose: 0, 0.35 and 0.52 μmol). Experiment 1 showed that EtOH and ACD supported appetitive conditioning independently of prenatal treatments. In Experiment 2, latency to display motor activity was altered only in neonates prenatally treated with water and challenged with the highest ACD dose. Prenatal EtOH experience results in tolerance to ACD's motor activity effects. These results show early susceptibility to ACD's appetitive effects and attenuation of motor effects as a function of prenatal history with EtOH, within a stage in development where brain ACD production seems higher than later in life. PMID:23785319

  18. Acetaldehyde reinforcement and motor reactivity in newborns with or without a prenatal history of alcohol exposure.

    PubMed

    March, Samanta M; Culleré, Marcela E; Abate, Paula; Hernández, José I; Spear, Norman E; Molina, Juan C

    2013-01-01

    Animal models have shown that early ontogeny seems to be a period of enhanced affinity to ethanol. Interestingly, the catalase system that transforms ethanol (EtOH) into acetaldehyde (ACD) in the brain, is more active in the perinatal rat compared to adults. ACD has been found to share EtOH's behavioral effects. The general purpose of the present study was to assess ACD motivational and motor effects in newborn rats as a function of prenatal exposure to EtOH. Experiment 1 evaluated if ACD (0.35 μmol) or EtOH (0.02 μmol) supported appetitive conditioning in newborn pups prenatally exposed to EtOH. Experiment 2 tested if prenatal alcohol exposure modulated neonatal susceptibility to ACD's motor effects (ACD dose: 0, 0.35 and 0.52 μmol). Experiment 1 showed that EtOH and ACD supported appetitive conditioning independently of prenatal treatments. In Experiment 2, latency to display motor activity was altered only in neonates prenatally treated with water and challenged with the highest ACD dose. Prenatal EtOH experience results in tolerance to ACD's motor activity effects. These results show early susceptibility to ACD's appetitive effects and attenuation of motor effects as a function of prenatal history with EtOH, within a stage in development where brain ACD production seems higher than later in life.

  19. Human exposure to fluorotelomer alcohols, perfluorooctane sulfonate and perfluorooctanoate via house dust in Bavaria, Germany.

    PubMed

    Xu, Zhenlan; Fiedler, Stefan; Pfister, Gerd; Henkelmann, Bernhard; Mosch, Christine; Völkel, Wolfgang; Fromme, Hermann; Schramm, Karl-Werner

    2013-01-15

    This study aimed at investigating the presence and distribution of fluorotelomer alcohols (FTOHs), perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in house dust to evaluate human exposure to these compounds via dust ingestion. 31 house dust samples were collected from Bavaria, Germany and analyzed for 4:2, 6:2, 8:2 and 10:2 FTOH, PFOS and PFOA. PFOA was the dominant compound in 79% of the dust samples, followed by PFOS and 8:2 FTOH, while 4:2 FTOH was not detected in any samples. The total concentration of per- and polyfluorinated compounds (PFCs) varied from 32.2 to 2456 ng/g. In addition, the total ingestion rate for PFCs was 0.4-135 ng/d for adults and 5.1-246 ng/d for toddlers, and the highest 8:2 FTOH-based PFOA intake via indoor dust was 0.24 ng/d for adults and 0.44 ng/d for toddlers. Overall, the results of this study demonstrate that dust ingestion is a minor pathway for human exposure to these PFCs; the PFC ingestion via indoor dust is generally low, and only under a worst scenario high intakes have to be expected for toddlers.

  20. Prenatal Alcohol Exposure Affects Progenitor Cell Numbers in Olfactory Bulbs and Dentate Gyrus of Vervet Monkeys

    PubMed Central

    Burke, Mark W.; Inyatkin, Alexey; Ptito, Maurice; Ervin, Frank R.; Palmour, Roberta M.

    2016-01-01

    Fetal alcohol exposure (FAE) alters hippocampal cell numbers in rodents and primates, and this may be due, in part, to a reduction in the number or migration of neuronal progenitor cells. The olfactory bulb exhibits substantial postnatal cellular proliferation and a rapid turnover of newly formed cells in the rostral migratory pathway, while production and migration of postnatal neurons into the dentate gyrus may be more complex. The relatively small size of the olfactory bulb, compared to the hippocampus, potentially makes this structure ideal for a rapid analysis. This study used the St. Kitts vervet monkey (Chlorocebus sabeus) to (1) investigate the normal developmental sequence of post-natal proliferation in the olfactory bulb and dentate gyrus and (2) determine the effects of naturalistic prenatal ethanol exposure on proliferation at three different ages (neonate, five months and two years). Using design-based stereology, we found an age-related decrease of actively proliferating cells in the olfactory bulb and dentate gyrus for both control and FAE groups. Furthermore, at the neonatal time point, the FAE group had fewer actively proliferating cells as compared to the control group. These data are unique with respect to fetal ethanol effects on progenitor proliferation in the primate brain and suggest that the olfactory bulb may be a useful structure for studies of cellular proliferation. PMID:27801790

  1. Mechanism for prevention of alcohol-induced liver injury by dietary methyl donors.

    PubMed

    Powell, Christine L; Bradford, Blair U; Craig, Christopher Patrick; Tsuchiya, Masato; Uehara, Takeki; O'Connell, Thomas M; Pogribny, Igor P; Melnyk, Stepan; Koop, Dennis R; Bleyle, Lisa; Threadgill, David W; Rusyn, Ivan

    2010-05-01

    Alcohol-induced liver injury (ALI) has been associated with, among other molecular changes, abnormal hepatic methionine metabolism, resulting in decreased levels of S-adenosylmethionine (SAM). Dietary methyl donor supplements such as SAM and betaine mitigate ALI in animal models; however, the mechanisms of protection remain elusive. It has been suggested that methyl donors may act via attenuation of alcohol-induced oxidative stress. We hypothesized that the protective action of methyl donors is mediated by an effect on the oxidative metabolism of alcohol in the liver. Male C57BL/6J mice were administered a control high-fat diet or diet enriched in methyl donors with or without alcohol for 4 weeks using the enteral alcohol feeding model. As expected, attenuation of ALI and an increase in reduced glutathione:oxidized glutathione ratio were achieved with methyl donor supplementation. Interestingly, methyl donors led to a 35% increase in blood alcohol elimination rate, and while there was no effect on alcohol metabolism in the stomach, a profound effect on liver alcohol metabolism was observed. The catalase-dependent pathway of alcohol metabolism was induced, yet the increase in CYP2E1 activity by alcohol was blunted, which may be mitigating production of oxidants. Additional factors contributing to the protective effects of methyl donors in ALI were increased activity of low- and high-K(m) aldehyde dehydrogenases leading to lower hepatic acetaldehyde, maintenance of the efficient mitochondrial energy metabolism, and promotion of peroxisomal beta-oxidation. Profound changes in alcohol metabolism represent additional important mechanism of the protective effect of methyl donors in ALI.

  2. Dysbiosis-induced intestinal inflammation activates TNFRI and mediates alcoholic liver disease in mice

    PubMed Central

    Chen, Peng; Stärkel, Peter; Turner, Jerrold R.; Ho, Samuel B.; Schnabl, Bernd

    2014-01-01

    Intestinal barrier dysfunction is an important contributor to alcoholic liver disease. Translocated microbial products trigger an inflammatory response in the liver and contribute to steatohepatitis. Our aim was to investigate mechanisms of barrier disruption following chronic alcohol feeding. A Lieber-DeCarli model was used to induce intestinal dysbiosis, increased intestinal permeability and liver disease in mice. Alcohol feeding for 8 weeks induced intestinal inflammation in the jejunum, which is characterized by an increased number of TNFα producing monocytes and macrophages. These findings were confirmed in duodenal biopsies from patients with chronic alcohol abuse. Intestinal decontamination with non-absorbable antibiotics restored eubiosis, decreased intestinal inflammation and permeability, and reduced alcoholic liver disease in mice. TNF-receptor I (TNFRI) mutant mice were protected from intestinal barrier dysfunction and alcoholic liver disease. To investigate whether TNFRI on intestinal epithelial cells mediates intestinal barrier dysfunction and alcoholic liver disease, we used TNFRI mutant mice carrying a conditional gain-of-function allele for this receptor. Reactivation of TNFRI on intestinal epithelial cells resulted in increased intestinal permeability and liver disease that is similar to wild type mice after alcohol feeding, suggesting that enteric TNFRI promotes intestinal barrier dysfunction. Myosin light chain kinase (MLCK) is a downstream target of TNFα and was phosphorylated in intestinal epithelial cells following alcohol administration. Using MLCK deficient mice, we further demonstrate a partial contribution of MLCK to intestinal barrier dysfunction and liver disease following chronic alcohol feeding. In conclusion, dysbiosis-induced intestinal inflammation and TNFRI signaling on intestinal epithelial cells are mediating a disruption of the intestinal barrier. Therefore, intestinal TNFRI is a crucial mediator of alcoholic liver disease

  3. The Potential Impact of a “No-Buy” List on Youth Exposure to Alcohol Advertising on Cable Television

    PubMed Central

    Ross, Craig S.; Brewer, Robert D.; Jernigan, David H.

    2016-01-01

    Objective: The purpose of this study was to outline a method to improve alcohol industry compliance with its self-regulatory advertising placement guidelines on television with the goal of reducing youth exposure to noncompliant advertisements. Method: Data were sourced from Nielsen (The Nielsen Company, New York, NY) for all alcohol advertisements on television in the United States for 2005–2012. A “no-buy” list, that is a list of cable television programs and networks to be avoided when purchasing alcohol advertising, was devised using three criteria: avoid placements on programs that were noncompliant in the past (serially noncompliant), avoid placements on networks at times of day when youth make up a high proportion of the audience (high-risk network dayparts), and use a “guardbanded” (or more restrictive) composition guideline when placing ads on low-rated programs (low rated). Results: Youth were exposed to 15.1 billion noncompliant advertising impressions from 2005 to 2012, mostly on cable television. Together, the three no-buy list criteria accounted for 99% of 12.9 billion noncompliant advertising exposures on cable television for youth ages 2–20 years. When we evaluated the no-buy list criteria sequentially and mutually exclusively, serially noncompliant ads accounted for 67% of noncompliant exposure, high-risk network-daypart ads accounted for 26%, and low rated ads accounted for 7%. Conclusions: These findings suggest that the prospective use of the no-buy list criteria when purchasing alcohol advertising could eliminate most noncompliant advertising exposures and could be incorporated into standard post-audit procedures that are widely used by the alcohol industry in assessing exposure to television advertising. PMID:26751350

  4. Molecular mechanisms of synaptic remodeling in alcoholism.

    PubMed

    Kyzar, Evan J; Pandey, Subhash C

    2015-08-05

    Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the "dark side" of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism.

  5. Association between alcohol-induced erythrocyte membrane alterations and hemolysis in chronic alcoholics

    PubMed Central

    Bulle, Saradamma; Reddy, Vaddi Damodara; Padmavathi, Pannuru; Maturu, Paramahamsa; Puvvada, Pavan Kumar; Nallanchakravarthula, Varadacharyulu

    2017-01-01

    The present study aimed to understand the association between erythrocyte membrane alterations and hemolysis in chronic alcoholics. Study was conducted on human male volunteers aged between 35–45 years with a drinking history of 8–10 years. Results showed that plasma marker enzymes AST, ALT, ALP and γGT were increased in alcoholic subjects. Plasma and erythrocyte membrane lipid peroxidation, erythrocyte lysate nitric oxide (NOx) levels were also increased significantly in alcoholics. Furthermore, erythrocyte membrane protein carbonyls, total cholesterol, phospholipid and cholesterol/phospholipid (C/P) ratio were increased in alcoholics. SDS-PAGE analysis of erythrocyte membrane proteins revealed that increased density of band 3, protein 4.2, 4.9, actin and glycophorins, whereas glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and glycophorin A showed slight increase, however, decreased ankyrin with no change in spectrins (α and β) and protein 4.1 densities were observed in alcoholics. Moreover, alcoholics red blood cells showed altered morphology with decreased resistance to osmotic hemolysis. Increased hemolysis showed strong positive association with lipid peroxidation (r = 0.703, p<0.05), protein carbonyls (r = 0.754, p<0.05), lysate NOx (r = 0.654, p<0.05) and weak association with C/P ratio (r = 0.240, p<0.05). Bottom line, increased lipid and protein oxidation, altered membrane C/P ratio and membrane cytoskeletal protein profile might be responsible for the increased hemolysis in alcoholics. PMID:28163384

  6. Association between alcohol-induced erythrocyte membrane alterations and hemolysis in chronic alcoholics.

    PubMed

    Bulle, Saradamma; Reddy, Vaddi Damodara; Padmavathi, Pannuru; Maturu, Paramahamsa; Puvvada, Pavan Kumar; Nallanchakravarthula, Varadacharyulu

    2017-01-01

    The present study aimed to understand the association between erythrocyte membrane alterations and hemolysis in chronic alcoholics. Study was conducted on human male volunteers aged between 35-45 years with a drinking history of 8-10 years. Results showed that plasma marker enzymes AST, ALT, ALP and γGT were increased in alcoholic subjects. Plasma and erythrocyte membrane lipid peroxidation, erythrocyte lysate nitric oxide (NOx) levels were also increased significantly in alcoholics. Furthermore, erythrocyte membrane protein carbonyls, total cholesterol, phospholipid and cholesterol/phospholipid (C/P) ratio were increased in alcoholics. SDS-PAGE analysis of erythrocyte membrane proteins revealed that increased density of band 3, protein 4.2, 4.9, actin and glycophorins, whereas glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and glycophorin A showed slight increase, however, decreased ankyrin with no change in spectrins (α and β) and protein 4.1 densities were observed in alcoholics. Moreover, alcoholics red blood cells showed altered morphology with decreased resistance to osmotic hemolysis. Increased hemolysis showed strong positive association with lipid peroxidation (r = 0.703, p<0.05), protein carbonyls (r = 0.754, p<0.05), lysate NOx (r = 0.654, p<0.05) and weak association with C/P ratio (r = 0.240, p<0.05). Bottom line, increased lipid and protein oxidation, altered membrane C/P ratio and membrane cytoskeletal protein profile might be responsible for the increased hemolysis in alcoholics.

  7. Alcoholic beverages induce superconductivity in FeTe1 - xSx

    NASA Astrophysics Data System (ADS)

    Deguchi, K.; Mizuguchi, Y.; Kawasaki, Y.; Ozaki, T.; Tsuda, S.; Yamaguchi, T.; Takano, Y.

    2011-05-01

    We found that hot alcoholic beverages were effective in inducing superconductivity in FeTe0.8S0.2. Heating the FeTe0.8S0.2 compound in various alcoholic beverages enhances the superconducting properties compared to a pure water-ethanol mixture as a control. Heating with red wine for 24 h leads to the largest shielding volume fraction of 62.4% and the highest zero resistivity temperature of 7.8 K. Some components present in alcoholic beverages, other than water and ethanol, have the ability to induce superconductivity in the FeTe0.8S0.2 compound.

  8. Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

    PubMed

    Banerjee, Atrayee; Abdelmegeed, Mohamed A; Jang, Sehwan; Song, Byoung-Joon

    2015-01-01

    The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT) or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH) (3.5 g/kg/dose oral gavages at 12-h intervals) or dextrose (Control). Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4), leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1) were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART), are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

  9. Abnormal brain activation during working memory in children with prenatal exposure to drugs of abuse: the effects of methamphetamine, alcohol, and polydrug exposure.

    PubMed

    Roussotte, Florence F; Bramen, Jennifer E; Nunez, S Christopher; Quandt, Lorna C; Smith, Lynne; O'Connor, Mary J; Bookheimer, Susan Y; Sowell, Elizabeth R

    2011-02-14

    Structural and metabolic abnormalities in fronto-striatal structures have been reported in children with prenatal methamphetamine (MA) exposure. The current study was designed to quantify functional alterations to the fronto-striatal circuit in children with prenatal MA exposure using functional magnetic resonance imaging (fMRI). Because many women who use MA during pregnancy also use alcohol, a known teratogen, we examined 50 children (age range 7-15), 19 with prenatal MA exposure, 15 of whom had concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but no MA exposure (ALC group), and 18 unexposed controls (CON group). We hypothesized that MA exposed children would demonstrate abnormal brain activation during a visuospatial working memory (WM) "N-Back" task. As predicted, the MAA group showed less activation than the CON group in many brain areas, including the striatum and frontal lobe in the left hemisphere. The ALC group showed less activation than the MAA group in several regions, including the right striatum. We found an inverse correlation between performance and activity in the striatum in both the CON and MAA groups. However, this relationship was significant in the caudate of the CON group but not the MAA group, and in the putamen of the MAA group but not the CON group. These findings suggest that structural damage in the fronto-striatal circuit after prenatal MA exposure leads to decreased recruitment of this circuit during a WM challenge, and raise the possibility that a rewiring of cortico-striatal networks may occur in children with prenatal MA exposure.

  10. Aberrant post-translational protein modifications in the pathogenesis of alcohol-induced liver injury

    PubMed Central

    Osna, Natalia A; Carter, Wayne G; Ganesan, Murali; Kirpich, Irina A; McClain, Craig J; Petersen, Dennis R; Shearn, Colin T; Tomasi, Maria L; Kharbanda, Kusum K

    2016-01-01

    It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular molecules thereby maintaining cellular hemostasis. Alcohol exposure significantly alters several of these post-translational modifications leading to impairments of many essential physiological processes. Here, we present new insights into novel modifications following ethanol exposure and their role in the initiation and progression of liver injury. This critical review condenses the proceedings of a symposium at the European Society for the Biomedical Research on Alcoholism Meeting held September 12-15, 2015, in Valencia, Spain. PMID:27468209

  11. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.

    PubMed

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming".

  12. Exposure to chronic alcohol accelerates development of wall stress and eccentric remodeling in rats with volume overload.

    PubMed

    Mouton, Alan J; Ninh, Van K; El Hajj, Elia C; El Hajj, Milad C; Gilpin, Nicholas W; Gardner, Jason D

    2016-08-01

    Chronic alcohol abuse is one of the leading causes of dilated cardiomyopathy (DCM) in the United States. Volume overload (VO) also produces DCM characterized by left ventricular (LV) dilatation and reduced systolic and diastolic function, eventually progressing to congestive heart failure. For this study, we hypothesized that chronic alcohol exposure would exacerbate cardiac dysfunction and remodeling due to VO. Aortocaval fistula surgery was used to induce VO, and compensatory cardiac remodeling was allowed to progress for either 3days (acute) or 8weeks (chronic). Alcohol was administered via chronic intermittent ethanol vapor (EtOH) for 2weeks before the acute study and for the duration of the 8week chronic study. Temporal alterations in LV function were assessed by echocardiography. At the 8week end point, pressure-volume loop analysis was performed by LV catheterization and cardiac tissue collected. EtOH did not exacerbate LV dilatation (end-systolic and diastolic diameter) or systolic dysfunction (fractional shortening, ejection fraction) due to VO. The combined stress of EtOH and VO decreased the eccentric index (posterior wall thickness to end-diastolic diameter ratio), increased end-diastolic pressure (EDP), and elevated diastolic wall stress. VO also led to increases in posterior wall thickness, which was not observed in the VO+EtOH group, and wall thickness significantly correlated with LV BNP expression. VO alone led to increases in interstitial collagen staining (picrosirius red), which while not statistically significant, tended to be decreased by EtOH. VO increased LV collagen I protein expression, whereas in rats with VO+EtOH, LV collagen I was not elevated relative to Sham. The combination of VO and EtOH also led to increases in LV collagen III expression relative to Sham. Rats with VO+EtOH had significantly lower collagen I/III ratio than rats with VO alone. During the acute remodeling phase of VO (3days), VO significantly increased collagen III

  13. Alcohol intoxications during adolescence increase motivation for alcohol in adult rats and induce neuroadaptations in the nucleus accumbens.

    PubMed

    Alaux-Cantin, Stéphanie; Warnault, Vincent; Legastelois, Rémi; Botia, Béatrice; Pierrefiche, Olivier; Vilpoux, Catherine; Naassila, Mickaël

    2013-04-01

    Adolescent alcohol binge drinking constitutes a major vulnerability factor to develop alcoholism. However, mechanisms underlying this susceptibility remain unknown. We evaluated the effect of adolescent binge-like ethanol intoxication on vulnerability to alcohol abuse in Sprague-Dawley rats. To model binge-like ethanol intoxication, every 2 days, rats received an ethanol injection (3.0 g/kg) for 2 consecutive days across 14 days either from postnatal day 30 (PND30) to 43 (early adolescence) or from PND 45 to PND 58 (late adolescence). In young adult animals, we measured free ethanol consumption in the two-bottle choice paradigm, motivation for ethanol in the operant self-administration task and both ethanol's rewarding and aversive properties in the conditioned place preference (CPP) and taste aversion (CTA) paradigms. While intermittent ethanol intoxications (IEI) during late adolescence had no effect on free-choice 10% ethanol consumption, we found that IEI during early adolescence promoted free-choice 10% ethanol consumption, enhanced motivation for ethanol in the self-administration paradigm and induced a loss of both ethanol-induced CPP and CTA in young adults. No modification in either sucrose self-administration or amphetamine-induced CPP was observed. As the nucleus accumbens (Nac) is particularly involved in addictive behavior, we analyzed IEI-induced long-term neuroadaptations in the Nac using c-Fos immunohistochemistry and an array of neurotransmission-related genes. This vulnerability to ethanol abuse was associated with a lower c-Fos immunoreactivity in the Nac and enduring alterations of the expression of Penk and Slc6a4, 2 neurotransmission-related genes that have been shown to play critical roles in the behavioral effects of ethanol and alcoholism.

  14. Effect of Prazosin and Naltrexone on Script Induced Alcohol Craving in Veterans with Alcohol Use Disorders with and without Co-occurring PTSD

    DTIC Science & Technology

    2015-01-01

    AWARD NUMBER: W81XWH-14-1-0025 TITLE: Effect of Prazosin and Naltrexone on Script Induced Alcohol Craving in Veterans with Alcohol Use...2015 2. REPORT TYPE Annual 3. DATES COVERED 4 Dec 2013 – 3 Dec 2014 4. Effect of Prazosin and Naltrexone on Script Induced Alcohol Craving in...Veterans with Alcohol Use Disorders with and without Co-occurring PTSD 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0025 5c. PROGRAM ELEMENT NUMBER

  15. Alcohol affects goal commitment by explicitly and implicitly induced myopia.

    PubMed

    Sevincer, A Timur; Oettingen, Gabriele; Lerner, Tobias

    2012-05-01

    Alcohol commits people to personally important goals even if expectations of reaching the goals are low. To illuminate this effect, we used alcohol myopia theory, stating that alcohol intoxicated people disproportionally attend to the most salient aspects of a situation and ignore peripheral aspects. When low expectations of reaching an important goal were activated students who consumed alcohol were less committed than students who consumed a placebo. We observed less commitment regardless of whether low expectations were explicitly activated in a questionnaire (Study 1) or implicitly activated through subliminal priming (Study 2). The results imply that, intoxicated people commit to goals according to what aspects of a goal are activated either explicitly or implicitly.

  16. Affective cue-induced escalation of alcohol self-administration and increased 22-kHz ultrasonic vocalizations during alcohol withdrawal: role of kappa-opioid receptors.

    PubMed

    Berger, Anthony L; Williams, Angela M; McGinnis, Molly M; Walker, Brendan M

    2013-03-01

    Negative affect promotes dysregulated alcohol consumption in non-dependent and alcohol-dependent animals, and cues associated with negative affective states induce withdrawal-like symptoms in rats. This study was designed to test the hypotheses that: (1) the kappa-opioid receptor (KOR) system mediates phenotypes related to alcohol withdrawal and withdrawal-like negative affective states and (2) cues associated with negative affective states would result in dysregulated alcohol consumption when subsequently presented alone. To accomplish these goals, intracerebroventricular infusion of the KOR antagonist nor-binaltorphimine (nor-BNI) was assessed for the ability to attenuate the increase in 22-kHz ultrasonic vocalizations (USVs) associated with alcohol withdrawal and KOR activation in adult male wistar rats. Furthermore, cues associated with a KOR agonist-induced negative affective state were assessed for the ability to dysregulate alcohol consumption and the efficacy of intracerebroventricular KOR antagonism to reduce such dysregulation was evaluated. KOR antagonism blocked the increased number of 22-kHz USVs observed during acute alcohol withdrawal and a KOR agonist (U50,488) resulted in a nor-BNI reversible increase in 22-kHz USVs (mimicking an alcohol-dependent state). Additionally, cues associated with negative affective states resulted in escalated alcohol self-administration, an effect that was nor-BNI sensitive. Taken together, this study implicates negative affective states induced by both alcohol withdrawal and conditioned stimuli as being produced, in part, by activity of the DYN/KOR system.

  17. Mechanisms of Alcohol Induced Effects on Cellular Cholesterol Dynamics

    DTIC Science & Technology

    2004-09-01

    lipids to SCP-2 tant role in the reduced risk of coronary heart disease in with cholesterol binding being most affected [3]. The asso- moderate alcohol...Avdulov NA, Chochina SV, lgbavboa U, Wood 234:25-33;1976. lipoproteins and coronary heart disease : The WG. Cholesterol effmux to high density lipopro... Cholesterol Efflux in Human Aortic Cells 3 Risk of coronary heart disease (CHD) morbidity and mortality is reduced by moderate alcohol consumption

  18. The effects of acute alcohol exposure on the response properties of neurons in visual cortex area 17 of cats

    SciTech Connect

    Chen Bo; Xia Jing; Li Guangxing; Zhou Yifeng

    2010-03-15

    Physiological and behavioral studies have demonstrated that a number of visual functions such as visual acuity, contrast sensitivity, and motion perception can be impaired by acute alcohol exposure. The orientation- and direction-selective responses of cells in primary visual cortex are thought to participate in the perception of form and motion. To investigate how orientation selectivity and direction selectivity of neurons are influenced by acute alcohol exposure in vivo, we used the extracellular single-unit recording technique to examine the response properties of neurons in primary visual cortex (A17) of adult cats. We found that alcohol reduces spontaneous activity, visual evoked unit responses, the signal-to-noise ratio, and orientation selectivity of A17 cells. In addition, small but detectable changes in both the preferred orientation/direction and the bandwidth of the orientation tuning curve of strongly orientation-biased A17 cells were observed after acute alcohol administration. Our findings may provide physiological evidence for some alcohol-related deficits in visual function observed in behavioral studies.

  19. Ethanol exposure induces a delay in the reacquisition of function during head regeneration in Schmidtea mediterranea.

    PubMed

    Lowe, Jesse R; Mahool, Tyler D; Staehle, Mary M

    2015-01-01

    Prenatal exposure to ethanol affects neurodevelopmental processes, leading to a variety of physical and cognitive impairments collectively termed Fetal Alcohol Spectrum Disorders (FASD). The molecular level ethanol-induced alterations that underlie FASD are poorly understood and are difficult to study in mammals. Ethanol exposure has been shown to affect regulation and differentiation of embryonic stem cells in vitro, suggesting that in vivo effects such as FASD could arise from similar alterations of stem cells. In this study, we hypothesize that ethanol exposure affects head regeneration and neuroregeneration in the Schmidtea mediterranea planarian. S. mediterranea freshwater flatworms have remarkable regenerative abilities arising from an abundant population of pluripotent adult somatic stem cells known as neoblasts. Here, we evaluated the mobility-normalized photophobic behavior of ethanol-exposed planaria as an indicator of cognitive function in intact and head-regenerating worms. Our studies show that exposure to 1% ethanol induces a delay in the reacquisition of behavior during head regeneration that cannot be attributed to the effect of ethanol on intact worms. This suggests that the S. mediterranea planarian could provide insight into conserved neurodevelopmental processes that are affected by ethanol and that lead to FASD in humans.

  20. Frontostriatal connectivity in children during working memory and the effects of prenatal methamphetamine, alcohol, and polydrug exposure.

    PubMed

    Roussotte, Florence F; Rudie, Jeffrey D; Smith, Lynne; O'Connor, Mary J; Bookheimer, Susan Y; Narr, Katherine L; Sowell, Elizabeth R

    2012-01-01

    Various abnormalities in frontal and striatal regions have been reported in children with prenatal alcohol and/or methamphetamine exposure. In a recent fMRI study, we observed a correlation between accuracy on a working-memory task and functional activation in the putamen in children with prenatal methamphetamine and polydrug exposure. Because the putamen is part of the corticostriatal motor loop whereas the caudate is involved in the executive loop, we hypothesized that a loss of segregation between distinct corticostriatal networks may occur in these participants. The current study was designed to test this hypothesis using functional connectivity MRI. We examined 50 children ranging in age from 7 to 15, including 19 with prenatal methamphetamine exposure (15 of whom had concomitant prenatal alcohol exposure), 13 with prenatal exposure to alcohol but not methamphetamine, and 18 unexposed controls. We measured the coupling between blood oxygenation level dependent (BOLD) fluctuations during a working-memory task in four striatal seed regions and those in the rest of the brain. We found that the putamen seeds showed increased connectivity with frontal brain regions involved in executive functions while the caudate seeds showed decreased connectivity with some of these regions in both groups of exposed subjects compared to controls. These findings suggest that localized brain abnormalities resulting from prenatal exposure to alcohol and/or methamphetamine lead to a partial rewiring of corticostriatal networks. These results represent important progress in the field, and could have substantial clinical significance in helping devise more targeted treatments and remediation strategies designed to better serve the needs of this population.

  1. Comparative assessments of the effects of alcohol exposure on fetal brain development using optical coherence tomography and ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

    2013-02-01

    The developing fetal brain is vulnerable to a variety of environmental agents including maternal ethanol consumption. Preclinical studies on the development and amelioration of fetal teratology would be significantly facilitated by the application of high resolution imaging technologies like optical coherence tomography (OCT) and high-frequency ultrasound (US). This study investigates the ability of these imaging technologies to measure the effects of maternal ethanol exposure on brain development, ex vivo, in fetal mice. Pregnant mice at gestational day 12.5 were administered ethanol (3 g/Kg b.wt.) or water by intragastric gavage, twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and imaged. Three-dimensional images of the mice fetus brains were obtained by OCT and high-resolution US, and the volumes of the left and right ventricles of the brain were measured. Ethanol-exposed fetuses exhibited a statistically significant, 2-fold increase in average left and right ventricular volumes compared with the ventricular volume of control fetuses, with OCT-derived measures of 0.38 and 0.18 mm3, respectively, whereas the boundaries of the fetal mouse lateral ventricles were not clearly definable with US imaging. Our results indicate that OCT is a useful technology for assessing ventriculomegaly accompanying alcohol-induced developmental delay. This study clearly demonstrated advantages of using OCT for quantitative assessment of embryonic development compared with US imaging.

  2. Autophagy in Alcohol-Induced Multiorgan Injury: Mechanisms and Potential Therapeutic Targets

    PubMed Central

    Wang, Shaogui; Ni, Hong-Min; Huang, Heqing

    2014-01-01

    Autophagy is a genetically programmed, evolutionarily conserved intracellular degradation pathway involved in the trafficking of long-lived proteins and cellular organelles to the lysosome for degradation to maintain cellular homeostasis. Alcohol consumption leads to injury in various tissues and organs including liver, pancreas, heart, brain, and muscle. Emerging evidence suggests that autophagy is involved in alcohol-induced tissue injury. Autophagy serves as a cellular protective mechanism against alcohol-induced tissue injury in most tissues but could be detrimental in heart and muscle. This review summarizes current knowledge about the role of autophagy in alcohol-induced injury in different tissues/organs and its potential molecular mechanisms as well as possible therapeutic targets based on modulation of autophagy. PMID:25140315

  3. Military sexual trauma, combat exposure, and negative urgency as independent predictors of PTSD and subsequent alcohol problems among OEF/OIF veterans.

    PubMed

    Hahn, Austin M; Tirabassi, Christine K; Simons, Raluca M; Simons, Jeffrey S

    2015-11-01

    This study tested a path model of relationships between military sexual trauma (MST), combat exposure, negative urgency, posttraumatic stress disorder (PTSD) symptoms, and alcohol use and related problems. The sample consisted of 86 Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans who reported drinking at least one alcoholic beverage per week. PTSD mediated the relationships between MST and alcohol-related problems, negative urgency and alcohol-related problems, and combat exposure and alcohol-related problems. In addition, negative urgency had a direct effect on alcohol problems. These results indicate that MST, combat exposure, and negative urgency independently predict PTSD symptoms and PTSD symptoms mediate their relationship with alcohol-related problems. Findings support previous literature on the effect of combat exposure and negative urgency on PTSD and subsequent alcohol-related problems. The current study also contributes to the limited research regarding the relationship between MST, PSTD, and alcohol use and related problems. Clinical interventions aimed at reducing emotional dysregulation and posttraumatic stress symptomology may subsequently improve alcohol-related outcomes.

  4. Military Sexual Trauma, Combat Exposure, and Negative Urgency as Independent Predictors of PTSD and Subsequent Alcohol Problems among OEF/OIF Veterans

    PubMed Central

    Tirabassi, Christine K.; Simons, Raluca M.; Simons, Jeffrey S.

    2015-01-01

    This study tested a path model of relationships between military sexual trauma (MST), combat exposure, negative urgency, posttraumatic stress disorder (PTSD) symptoms, and alcohol use and related problems. The sample consisted of 86 OEF/OIF veterans who reported drinking at least one alcoholic beverage per week. PTSD mediated the relationships between MST and alcohol-related problems, negative urgency and alcohol-related problems, as well as combat exposure and alcohol-related problems. In addition, negative urgency had a direct effect on alcohol problems. These results indicate that MST, combat exposure, and negative urgency independently predict PTSD symptoms and PTSD symptoms mediate their relationship with alcohol-related problems. Findings support previous literature on the effect of combat exposure and negative urgency on PTSD and subsequent alcohol-related problems. The current study also contributes to the limited research regarding the relationship between MST, PSTD, and alcohol use and related problems. Clinical interventions aimed at reducing emotional dysregulation and posttraumatic stress symptomology may subsequently improve alcohol related outcomes. PMID:26524279

  5. Prenatal ethanol exposure alters ethanol-induced Fos immunoreactivity and dopaminergic activity in the mesocorticolimbic pathway of the adolescent brain.

    PubMed

    Fabio, M C; Vivas, L M; Pautassi, R M

    2015-08-20

    Prenatal ethanol exposure (PEE) promotes alcohol intake during adolescence, as shown in clinical and pre-clinical animal models. The mechanisms underlying this effect of prenatal ethanol exposure on postnatal ethanol intake remain, however, mostly unknown. Few studies assessed the effects of moderate doses of prenatal ethanol on spontaneous and ethanol-induced brain activity on adolescence. This study measured, in adolescent (female) Wistar rats prenatally exposed to ethanol (0.0 or 2.0g/kg/day, gestational days 17-20) or non-manipulated (NM group) throughout pregnancy, baseline and ethanol-induced cathecolaminergic activity (i.e., colocalization of c-Fos and tyrosine hydroxylase) in ventral tegmental area (VTA), and baseline and ethanol-induced Fos immunoreactivity (ir) in nucleus accumbens shell and core (AcbSh and AcbC, respectively) and prelimbic (PrL) and infralimbic (IL) prefrontal cortex. The rats were challenged with ethanol (dose: 0.0, 1.25, 2.5 or 3.25g/kg, i.p.) at postnatal day 37. Rats exposed to vehicle prenatally (VE group) exhibited reduced baseline dopaminergic tone in VTA; an effect that was inhibited by prenatal ethanol exposure (PEE group). Dopaminergic activity in VTA after the postnatal ethanol challenge was greater in PEE than in VE or NM animals. Ethanol-induced Fos-ir at AcbSh was found after 1.25g/kg and 2.5g/kg ethanol, in VE and PEE rats, respectively. PEE did not alter ethanol-induced Fos-ir at IL but reduced ethanol-induced Fos-ir at PrL. These results suggest that prenatal ethanol exposure heightens dopaminergic activity in the VTA and alters the response of the mesocorticolimbic pathway to postnatal ethanol exposure. These effects may underlie the enhanced vulnerability to develop alcohol-use disorders of adolescents with a history of in utero ethanol exposure.

  6. Betaine supplementation reduces congenital defects after prenatal alcohol exposure (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Sheehan, Megan M.; Ma, Pei; Peterson, Lindsy M.; Linask, Kersti K.; Jenkins, Michael W.; Rollins, Andrew M.; Watanabe, Michiko

    2016-03-01

    Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. As high as 20-50% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects including outflow and valvuloseptal anomalies that can be life-threatening. Previously we established a model of PAE (modeling a single binge drinking episode) in the avian embryo and used optical coherence tomography (OCT) imaging to assay early-stage cardiac function/structure and late-stage cardiac defects. At early stages, alcohol/ethanol-exposed embryos had smaller cardiac cushions and increased retrograde flow. At late stages, they presented with gross morphological defects in the head and chest wall, and also exhibited smaller or abnormal atrio-ventricular (AV) valves, thinner interventricular septae (IVS), and smaller vessel diameters for the aortic trunk branches. In other animal models, the methyl donor betaine (found naturally in many foods such as wheat bran, quinoa, beets and spinach) ameliorates neurobehavioral deficits associated with PAE but the effects on heart structure are unknown. In our model of PAE, betaine supplementation led to a reduction in gross structural defects and appeared to protect against certain types of cardiac defects such as ventricular septal defects and abnormal AV valvular morphology. Furthermore, vessel diameters, IVS thicknesses and mural AV leaflet volumes were normalized while the septal AV leaflet volume was increased. These findings highlight the importance of betaine and potentially methylation levels in the prevention of PAE-related birth defects which could have significant implications for public health.

  7. Exposure to the Lebanon War of 2006 and effects on alcohol use disorders: The moderating role of childhood maltreatment☆

    PubMed Central

    Keyes, Katherine M.; Shmulewitz, Dvora; Greenstein, Eliana; McLaughlin, Kate; Wall, Melanie; Aharonovich, Efrat; Weizman, Abraham; Frisch, Amos; Spivak, Baruch; Grant, Bridget F.; Hasin, Deborah

    2013-01-01

    Background Civilian populations now comprise the majority of casualties in modern warfare, but effects of war exposure on alcohol disorders in the general population are largely unexplored. Accumulating literature indicates that adverse experiences early in life sensitize individuals to increased alcohol problems after adult stressful experiences. However, child and adult stressful experiences can be correlated, limiting interpretation. We examine risk for alcohol disorders among Israelis after the 2006 Lebanon War, a fateful event outside the control of civilian individuals and uncorrelated with childhood experiences. Further, we test whether those with a history of maltreatment are at greater risk for an alcohol use disorder after war exposure compared to those without such a history. Methods Adult household residents selected from the Israeli population register were assessed with a psychiatric structured interview; the analyzed sample included 1306 respondents. War measures included self-reported days in an exposed region. Results Among those with a history of maltreatment, those in a war-exposed region for 30+ days had 5.3 times the odds of subsequent alcohol disorders compared to those exposed 0 days (95%C.I. 1.01–27.76), controlled for relevant confounders; the odds ratio for those without this history was 0.5 (95%C.I. 0.25–1.01); test for interaction: X2 = 5.28, df = 1, P = 0.02. Conclusions Experiencing a fateful stressor outside the control of study participants, civilian exposure to the 2006 Lebanon War, is associated with a heightened the risk of alcohol disorders among those with early adverse childhood experiences. Results suggest that early life experiences may sensitize individuals to adverse health responses later in life. PMID:24262650

  8. Enriched environment attenuates changes in water-maze performance and BDNF level caused by prenatal alcohol exposure

    PubMed Central

    Tipyasang, Rungpiyada; Kunwittaya, Sarun; Mukda, Sujira; Kotchabhakdi, Nittaya J.; Kotchabhakdi, Naiphinich

    2014-01-01

    Prenatal exposure to alcohol can result in fetal alcohol syndrome (FAS), characterized by significant changes in the physiology, structural plasticity of hippocampal function, including long-term deficits in learning and memory. Environmental enrichment has long been known to improve motor and cognitive function levels, causes several neurochemical and morphological alterations in the brain. Therefore, the effects of environmental enrichment on the neurobehavioral and neurotrophic changes in mice exposed prenatally to alcohol were investigated in this study. The pregnant dams were given 25 % ethanol (w/v) or isocaloric sucrose by liquid diet from gestation day 7 to 20. After weaning on postnatal day 28, offspring were exposed to standard cage (CC, CFAS) or enriched living conditions (CE, EFAS) for 8 weeks. Neurobehavioral studies both on hippocampus-dependent spatial learning and place and cue learning strategy, a striatum-dependent test, were measured by the Morris water maze task. Moreover, the reverse-transcriptase polymerase chain reaction (RT-PCR) technique was also used in order to study the expression of brain-derived neurotrophic factor (BDNF) level in both the hippocampus and striatum of mice. Neurobehavioral studies show that animals exposed prenatally to alcohol were impaired as shown in both hippocampal-dependent spatial/place and striatal-dependent response/cue learning tests. Moreover, the levels of BDNF expression both in the hippocampus and striatum of mice were also decreased. Interestingly, environmental enrichment can ameliorate the effects of prenatal alcohol exposure both on the neurobehavioral and neurotrophic levels. These observations indicated that enriched environment attenuated memory impairment of prenatal alcohol exposure both in hippocampal and striatal circuitry. PMID:26417281

  9. Exposure to tobacco, alcohol and drugs of abuse during pregnancy. A study of prevalence among pregnant women in Malaga (Spain).

    PubMed

    Blasco-Alonso, Marta; González-Mesa, Ernesto; Gálvez Montes, Milagros; Lozano Bravo, Isabel; Merino Galdón, Federico; Cuenca Campos, Francisco; Marín Schiaffino, Gema; Pérez Torres, Sergio; Herrera Peral, José; Bellido Estévez, Inmaculada

    2015-06-17

    The prevalence of substance abuse in women who become pregnant is similar to that of the general population, resulting in a high fetal exposure rate during the most vulnerable period regarding neurodevelopment and organogenesis. The present study was intended to assess the level of prenatal exposure to tobacco, alcohol or illicit drugs in the city of Málaga (Spain). It was designed as a cross-sectional study, and based on the anonymous self-reports of participants. A total of 451 pregnant women were recruited in the first, second or third trimester. The prevalence in each of the quarters respectively was 21.2%, 18.5% and 13.3% for smoking, 40.7%, 23.1% and 17.1% for alcohol and 4.8%, 1.9% and 1.2% for cannabis. We also found that a higher educational level was associated with a lower consumption of tobacco (RR 0.659 [0.537-0.810] p<0.0001) and greater exposure to alcohol (RR 1.87 [1.30-2.69] p<0.0007). These results, particularly in regard to alcohol intake, are sufficiently alarming to alert obstetric care providers about the need to implement preventive measures.

  10. Role of hypoxia inducing factor-1β in alcohol-induced autophagy, steatosis and liver injury in mice.

    PubMed

    Ni, Hong-Min; Bhakta, Amar; Wang, Shaogui; Li, Zhenrui; Manley, Sharon; Huang, Heqing; Copple, Bryan; Ding, Wen-Xing

    2014-01-01

    Chronic alcohol causes liver hypoxia and steatosis, which eventually develops into alcoholic liver disease (ALD). While it has been known that alcohol consumption activates hepatic hypoxia inducing factor-1α (HIF-1α), conflicting results regarding the role of HIF-1α in alcohol-induced liver injury and steatosis in mice have been reported. In the present study, we aimed to use hepatocyte-specific HIF-1β knockout mice to eliminate the possible compensatory effects of the single knockout of the 1α subunit of HIF to study the role of HIFs in ALD. C57BL/6 wild type mice were treated with acute ethanol to mimic human binge drinking. Matched wild-type and hepatocyte specific HIF-1β knockout mice were also subjected to a recently established Gao-binge alcohol model to mimic chronic plus binge conditions, which is quite common in human alcoholics. We found that acute alcohol treatment increased BNIP3 and BNIP3L/NIX expression in primary cultured hepatocytes and in mouse livers, suggesting that HIF may be activated in these models. We further found that hepatocyte-specific HIF-1β knockout mice developed less steatosis and liver injury following the Gao-binge model or acute ethanol treatment compared with their matched wild type mice. Mechanistically, protection against Gao-binge treatment-induced steatosis and liver injury was likely associated with increased FoxO3a activation and subsequent induction of autophagy in hepatocyte-specific HIF-1β knockout mice.

  11. Preventing gut leakiness by oats supplementation ameliorates alcohol-induced liver damage in rats.

    PubMed

    Keshavarzian, A; Choudhary, S; Holmes, E W; Yong, S; Banan, A; Jakate, S; Fields, J Z

    2001-11-01

    Only 30% of alcoholics develop liver disease (ALD) suggesting that additional factors are needed. Endotoxin is one such factor, but its etiology is unclear. Since the gut is the main source of endotoxin, we sought to determine whether an increase in intestinal permeability (leaky gut) is required for alcohol-induced endotoxemia and liver injury and whether the gut leakiness is preventable. For 10 weeks, rats received by gavage increasing alcohol doses (to 8 g/kg/day) and either oats (10 g/kg) or chow b.i.d. Intestinal permeability was then assessed by urinary excretion of lactulose and mannitol. Liver injury was evaluated histologically, biochemically (liver fat content), and by serum aminotransferase. Alcohol caused gut leakiness that was associated with both endotoxemia and liver injury. Oats prevented these changes. We conclude that chronic gavage of alcohol in rats is a simple experimental model that mimics key aspects of ALD, including endotoxemia and liver injury, and can be useful to study possible mechanisms of endotoxemia in ALD. Since preventing the gut leakiness by oats also prevented the endotoxemia and ameliorated liver damage in rat, our results suggest that alcohol-induced gut leakiness 1) may cause alcohol-induced endotoxemia and liver injury and 2) may be the critical cofactor in the 30% of alcoholics who develop ALD. Further studies are needed to determine whether ALD in humans can be prevented by preventing alcohol-induced gut leakiness, studies that should lead to the development of useful therapeutic agents for the prevention of ALD.

  12. Effects of Intermittent Alcohol Exposure on Emotion and Cognition: A Potential Role for the Endogenous Cannabinoid System and Neuroinflammation

    PubMed Central

    Sanchez-Marin, Laura; Pavon, Francisco J.; Decara, Juan; Suarez, Juan; Gavito, Ana; Castilla-Ortega, Estela; Rodriguez de Fonseca, Fernando; Serrano, Antonia

    2017-01-01

    Intermittent alcohol exposure is a common pattern of adolescent alcohol use that can lead to binge drinking episodes. Alcohol use is known to modulate the endocannabinoid system (ECS), which is involved in neuronal communication, neuroplasticity, neuroinflammation and behavior. Adolescent male Wistar rats were exposed to 4-week intermittent alcohol intoxication (3 g/kg injections for 4 days/week) or saline (N = 12 per group). After alcohol deprivation, adult rats were assessed for emotionality and cognition and the gene expression of the ECS and other factors related to behavior and neuroinflammation was examined in the brain. Alcohol-exposed rats exhibited anxiogenic-like responses and impaired recognition memory but no motor alterations. There were brain region-dependent changes in the mRNA levels of the ECS and molecular signals compared with control rats. Thus, overall, alcohol-exposed rats expressed higher mRNA levels of endocannabinoid synthetic enzymes (N-acyl-phosphatidylethanolamine phospholipase D and diacylglycerol lipases) in the medial-prefrontal cortex (mPFC) but lower mRNA levels in the amygdala. Furthermore, we observed lower mRNA levels of receptors CB1 CB2 and peroxisome proliferator-activated receptor-α in the striatum. Regarding neuropeptide signaling, alcohol-exposed rats displayed lower mRNA levels of the neuropeptide Y signaling, particularly NPY receptor-2, in the amygdala and hippocampus and higher mRNA levels of corticotropin-releasing factor in the hippocampus. Additionally, we observed changes of several neuroinflammation-related factors. Whereas, the mRNA levels of toll-like receptor-4, tumor necrosis factor-α, cyclooxygenase-2 and glial fibrillary acidic protein were significantly increased in the mPFC, the mRNA levels of cyclooxygenase-2 and glial fibrillary acidic protein were decreased in the striatum and hippocampus. However, nuclear factor-κβ mRNA levels were lower in the mPFC and striatum and allograft inflammatory factor-1

  13. Effects of Intermittent Alcohol Exposure on Emotion and Cognition: A Potential Role for the Endogenous Cannabinoid System and Neuroinflammation.

    PubMed

    Sanchez-Marin, Laura; Pavon, Francisco J; Decara, Juan; Suarez, Juan; Gavito, Ana; Castilla-Ortega, Estela; Rodriguez de Fonseca, Fernando; Serrano, Antonia

    2017-01-01

    Intermittent alcohol exposure is a common pattern of adolescent alcohol use that can lead to binge drinking episodes. Alcohol use is known to modulate the endocannabinoid system (ECS), which is involved in neuronal communication, neuroplasticity, neuroinflammation and behavior. Adolescent male Wistar rats were exposed to 4-week intermittent alcohol intoxication (3 g/kg injections for 4 days/week) or saline (N = 12 per group). After alcohol deprivation, adult rats were assessed for emotionality and cognition and the gene expression of the ECS and other factors related to behavior and neuroinflammation was examined in the brain. Alcohol-exposed rats exhibited anxiogenic-like responses and impaired recognition memory but no motor alterations. There were brain region-dependent changes in the mRNA levels of the ECS and molecular signals compared with control rats. Thus, overall, alcohol-exposed rats expressed higher mRNA levels of endocannabinoid synthetic enzymes (N-acyl-phosphatidylethanolamine phospholipase D and diacylglycerol lipases) in the medial-prefrontal cortex (mPFC) but lower mRNA levels in the amygdala. Furthermore, we observed lower mRNA levels of receptors CB1 CB2 and peroxisome proliferator-activated receptor-α in the striatum. Regarding neuropeptide signaling, alcohol-exposed rats displayed lower mRNA levels of the neuropeptide Y signaling, particularly NPY receptor-2, in the amygdala and hippocampus and higher mRNA levels of corticotropin-releasing factor in the hippocampus. Additionally, we observed changes of several neuroinflammation-related factors. Whereas, the mRNA levels of toll-like receptor-4, tumor necrosis factor-α, cyclooxygenase-2 and glial fibrillary acidic protein were significantly increased in the mPFC, the mRNA levels of cyclooxygenase-2 and glial fibrillary acidic protein were decreased in the striatum and hippocampus. However, nuclear factor-κβ mRNA levels were lower in the mPFC and striatum and allograft inflammatory factor-1

  14. Growing up with Parental Alcohol Abuse: Exposure to Childhood Abuse, Neglect, and Household Dysfunction.

    ERIC Educational Resources Information Center

    Dube, Shanta R.; Anda, Robert F.; Felitti, Vincent J.; Croft, Janet B.; Edwards, Valerie J.; Giles, Wayne H.

    2001-01-01

    A study involving 8,629 adults examined the association between parental alcohol abuse and child abuse, neglect, and other household dysfunction. Compared to households without alcohol abuse, the adjusted odds ratio for each category of adverse childhood experience was 2 to 13 times higher if parents abused alcohol. (Contains references.) (CR)

  15. Modulation of Intestinal Barrier and Bacterial Endotoxin Production Contributes to the Beneficial Effect of Nicotinic Acid on Alcohol-Induced Endotoxemia and Hepatic Inflammation in Rats

    PubMed Central

    Zhong, Wei; Li, Qiong; Zhang, Wenliang; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

    2015-01-01

    Alcohol consumption causes nicotinic acid deficiency. The present study was undertaken to determine whether dietary nicotinic acid supplementation provides beneficial effects on alcohol-induced endotoxin signaling and the possible mechanisms at the gut-liver axis. Male Sprague-Dawley rats were pair-fed the Lieber-DeCarli liquid diets containing ethanol or isocaloric maltose dextrin for eight weeks, with or without dietary supplementation with 750 mg/liter nicotinic acid. Chronic alcohol feeding elevated the plasma endotoxin level and activated hepatic endotoxin signaling cascade, which were attenuated by nicotinic acid supplementation. Alcohol consumption remarkably decreased the mRNA levels of claudin-1, claudin-5, and ZO-1 in the distal intestine, whereas nicotinic acid significantly up-regulated these genes. The concentrations of endotoxin, ethanol, and acetaldehyde in the intestinal contents were increased by alcohol exposure, and niacin supplementation reduced the intestinal endotoxin and acetaldehyde levels. Nicotinic acid supplementation upregulated the intestinal genes involved in aldehyde detoxification via transcriptional regulation. These results demonstrate that modulation of the intestinal barrier function and bacterial endotoxin production accounts for the inhibitory effects of nicotinic acid on alcohol-induced endotoxemia and hepatic inflammation. PMID:26501337

  16. Neurokinin-1 receptor antagonism attenuates neuronal activity triggered by stress-induced reinstatement of alcohol seeking

    PubMed Central

    Schank, J.R.; Nelson, B.S.; Damadzic, R.; Tapocik, J.D.; Yao, M.; King, C.E.; Rowe, K.E.; Cheng, K.; Rice, K.C.; Heilig, M.

    2015-01-01

    Substance P (SP) and its cognate neurokinin-1 receptor (NK1R) are involved in alcohol-related behaviors. We have previously reported that NK1R antagonism attenuates stress-induced reinstatement of alcohol seeking and suppresses escalated alcohol self-administration, but does not affect primary reinforcement or cue-induced reinstatement. Here, we administered an NK1R antagonist or vehicle prior to footshock-induced reinstatement of alcohol seeking, and mapped the resulting neuronal activation using Fos immunohistochemistry. As expected, vehicle treated animals exposed to footshock showed induction of Fos immunoreactivity in several regions of the brain stress circuitry, including the amygdala (AMG), nucleus accumbens (NAC), dorsal raphe nucleus (DR), prefrontal cortex (PFC), and bed nucleus of the stria terminalis (BNST). NK1R antagonism selectively suppressed the stress-induced increase in Fos in the DR and NAC shell. In the DR, Fos-induction by stress largely overlapped with tryptophan hydroxylase (TrpH), indicating activation of serotonergic neurons. Of NAC shell neurons activated during stress-induced reinstatement of alcohol seeking, about 30% co-expressed dynorphin (DYN), while 70% co-expressed enkephalin (ENK). Few (<1%) activated NAC shell neurons co-expressed choline acetyltransferase (ChAT), which labels the cholinergic interneurons of this region. Infusion of the NK1R antagonist L822429 into the NAC shell blocked stress-induced reinstatement of alcohol seeking. In contrast, L822429 infusion into the DR had no effect, suggesting that the influence of NK1R signaling on neuronal activity in the DR is indirect. Taken together, our results outline a potential pathway through which endogenous NK1R activation mediates stress-induced alcohol seeking. PMID:26188146

  17. Purple potato (Solanum tuberosum L.) anthocyanins attenuate alcohol-induced hepatic injury by enhancing antioxidant defense.

    PubMed

    Jiang, Zhihui; Chen, Chen; Wang, Jian; Xie, Wenyan; Wang, Meng; Li, Xinsheng; Zhang, Xiaoying

    2016-01-01

    Alcoholic liver disease (ALD) is a serious and challenging health issue. In the past decade, natural components possessing hepatoprotective properties have gained more attention for ALD intervention. In this study, the phytochemical components of anthocyanins from purple potato were assessed using UPLC-MS/MS, and the hepatoprotective effects of purple potato anthocyanins (PPAs) were investigated in the ALD mouse model. Serum and liver biochemical parameters were determined, along with histopathological changes in liver tissue. In addition, the major contributors to alcohol-induced oxidative stress were assessed. The results indicated that the levels of aspartate transaminase and alanine transaminase were lower in the serum of the PPA-treated group than the alcohol-treated group. PPAs significantly inhibited the reduction of total cholesterol and triglycerides. Higher levels of superoxide dismutase and reduced glutathione enzymes as well as a reduction in the formation of malondialdehyde occurred in mice fed with PPAs. In addition, PPAs protected against increased alcohol-induced levels and activity of cytochrome P450 2E1 (CYP2E1), which demonstrates the effects of PPAs against alcohol-induced oxidative stress and liver injury. This study suggests that PPAs could be an effective therapeutic agent in alcohol-induced liver injuries by inhibiting CYP2E1 expression and thereby strengthening antioxidant defenses.

  18. Central Pontine Myelinolysis Induced by Alcohol Withdrawal: A Case Report

    PubMed Central

    2017-01-01

    Central pontine myelinolysis (CPM) is a demyelinating disorder characterized by the loss of myelin in the center of the basis pons, and is mainly caused by the rapid correction of hyponatremia. We report the case of a young woman who presented with gait disturbance and alcohol withdrawal, and who was eventually diagnosed with CPM. Generally, the cause and pathogenesis of CPM in chronic alcoholics remain unclear. In this cases, the CPM may be unrelated to hyponatremia or its correction. However, it is possible that the osmotic pressure changes due to refeeding syndrome after alcohol withdrawal was the likely cause in this case. This case illustrates the need for avoiding hasty, and possibly incomplete diagnoses, and performing more intensive test procedures to ensure a correct diagnosis. PMID:28289647

  19. Acute alcohol exposure during mouse gastrulation alters lipid metabolism in placental and heart development: Folate prevention

    PubMed Central

    Han, Mingda

    2016-01-01

    Background Embryonic acute exposure to ethanol (EtOH), lithium, and homocysteine (HCy) induces cardiac defects at the time of exposure; folic acid (FA) supplementation protects normal cardiogenesis (Han et al., 2009, 2012; Serrano et al., 2010). Our hypothesis is that EtOH exposure and FA protection relate to lipid and FA metabolism during mouse cardiogenesis and placentation. Methods On the morning of conception, pregnant C57BL/6J mice were placed on either of two FA‐containing diets: a 3.3 mg health maintenance diet or a high FA diet of 10.5 mg/kg. Mice were injected a binge level of EtOH, HCy, or saline on embryonic day (E) 6.75, targeting gastrulation. On E15.5, cardiac and umbilical blood flow were examined by ultrasound. Embryonic cardiac tissues were processed for gene expression of lipid and FA metabolism; the placenta and heart tissues for neutral lipid droplets, or for medium chain acyl‐dehydrogenase (MCAD) protein. Results EtOH exposure altered lipid‐related gene expression on E7.5 in comparison to control or FA‐supplemented groups and remained altered on E15.5 similarly to changes with HCy, signifying FA deficiency. In comparison to control tissues, the lipid‐related acyl CoA dehydrogenase medium length chain gene and its protein MCAD were altered with EtOH exposure, as were neutral lipid droplet localization in the heart and placenta. Conclusion EtOH altered gene expression associated with lipid and folate metabolism, as well as neutral lipids, in the E15.5 abnormally functioning heart and placenta. In comparison to controls, the high FA diet protected the embryo and placenta from these effects allowing normal development. Birth Defects Research (Part A) 106:749–760, 2016. © 2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc. PMID:27296863

  20. Poly(vinyl alcohol) hydrogel coatings with tunable surface exposure of hydroxyapatite.

    PubMed

    Moreau, David; Villain, Arthur; Ku, David N; Corté, Laurent

    2014-01-01

    Insufficient bone anchoring is a major limitation of artificial substitutes for connective osteoarticular tissues. The use of coatings containing osseoconductive ceramic particles is one of the actively explored strategies to improve osseointegration and strengthen the bone-implant interface for general tissue engineering. Our hypothesis is that hydroxyapatite (HA) particles can be coated robustly on specific assemblies of PVA hydrogel fibers for the potential anchoring of ligament replacements. A simple dip-coating method is described to produce composite coatings made of microscopic hydroxyapatite (HA) particles dispersed in a poly(vinyl alcohol) (PVA) matrix. The materials are compatible with the requirements for implant Good Manufacturing Practices. They are applied to coat bundles of PVA hydrogel fibers used for the development of ligament implants. By means of optical and electronic microscopy, we show that the coating thickness and surface state can be adjusted by varying the composition of the dipping solution. Quantitative analysis based on backscattered electron microscopy show that the exposure of HA at the coating surface can be tuned from 0 to over 55% by decreasing the weight ratio of PVA over HA from 0.4 to 0.1. Abrasion experiments simulating bone-implant contact illustrate how the coating cohesion and wear resistance increase by increasing the content of PVA relative to HA. Using pullout experiments, we find that these coatings adhere well to the fiber bundles and detach by propagation of a crack inside the coating. These results provide a guide to select coated implants for anchoring artificial ligaments.

  1. Tobacco and alcohol use during pregnancy and risk of oral clefts. Occupational Exposure and Congenital Malformation Working Group.

    PubMed Central

    Lorente, C; Cordier, S; Goujard, J; Aymé, S; Bianchi, F; Calzolari, E; De Walle, H E; Knill-Jones, R

    2000-01-01

    OBJECTIVES: This study examined the relationship between maternal tobacco and alcohol consumption during the first trimester of pregnancy and oral clefts. METHODS: Data were derived from a European multicenter case-control study including 161 infants with oral clefts and 1134 control infants. RESULTS: Multivariate analyses showed an increased risk of cleft lip with or without cleft palate associated with smoking (odds ratio [OR] = 1.79, 95% confidence interval [CI] = 1.07, 3.04) and an increased risk of cleft palate associated with alcohol consumption (OR = 2.28, 95% CI = 1.02, 5.09). The former risk increased with the number of cigarettes smoked. CONCLUSIONS: This study provides further evidence of the possible role of prevalent environmental exposures such as tobacco and alcohol in the etiology of oral clefts. PMID:10705862

  2. Effect of diethylcarbamazine on chronic hepatic inflammation induced by alcohol in C57BL/6 mice.

    PubMed

    Santos Rocha, Sura Wanessa; Silva, Bruna Santos; Gomes, Fabiana Oliveira dos Santos; Soares e Silva, Amanda Karolina; Raposo, Catarina; Barbosa, Karla Patrícia Sousa; Torres, Dilênia de Oliveira Cipriano; dos Santos, Ana Célia Oliveira; Peixoto, Christina Alves

    2012-08-15

    Some pharmacological studies showed that diethylcarbamazine (DEC) interferes with the arachidonic acid metabolism, acting as an anti-inflammatory drug. The chronic alcohol consumption activates the hepatic inflammatory response associated to T-cell activation and overproduction of pro-inflammatory cytokines. The present work analyzed the anti-inflammatory effect of DEC on hepatic cells of alcoholic mice. Thirty-two male C57BL/6 mice were equally divided in the following groups: (a) control group (C), which received only water, (b) DEC-treated group, which received 50 mg/kg for 12 day (DEC50), (c) the alcoholic group (EtOH), submitted to only alcohol and (d) the alcohol-DEC treated group (EtOH50), submitted to alcohol plus DEC treatment after the induction of chronic alcoholism for 5 weeks. Biochemical analyses were performed and liver fragments were processed for light microscopy, transmission electron microscopy, immunohistochemical and western blot. The level of AST increased significantly in alcoholic group whereas a significant reduction of serum AST was detected in the EtOH50 group. Histological and ultrastructural analysis of alcoholic group showed evident hepatocellular damage, which was strikingly reduced in the alcoholic DEC-treated group. Immunohistochemistry results revealed highly expression of inflammatory markers as MDA, NF-κB, TNF-α, IL-6, VCAM and ICAM by the hepatic cells of the EtOH group; however no immunoreactivity for any of these cytokines was detected after DEC treatment. Western blot analyses showed increased MCP-1 and iNOS expression in EtOH group, which was significantly inhibited by DEC treatment. According to the present results, DEC can be a potential drug for the treatment of chronic inflammation induced by chronic alcoholism.

  3. The mechanism of alcoholic beverage induced superconductivity in Fe-chalcogenide compounds

    NASA Astrophysics Data System (ADS)

    Deguchi, Keita; Demura, Satoshi; Okazaki, Hiroyuki; Denholme, Saleem; Fujioka, Masaya; Ozaki, Toshinori; Yamaguchi, Takahide; Takeya, Hiroyuki; Takano, Yoshihiko

    2013-03-01

    We have clarified the mechanism of alcoholic beverage induced superconductivity in Fe-chalcogenide compounds. Previously we reported that the bulk superconductivity in Fe-based compounds Fe(Te, Se) and Fe(Te, S) is achieved by heating in alcoholic beverages. However, the exact mechanism of how they act to enhance the superconductivity in the compounds remains unsolved. To understand the effect of alcoholic beverage treatment, we investigated the mechanism using a technology of metabolomic analysis. We found that weak acid in alcoholic beverages has the ability to deintercalate the excess Fe, which is not in favor of superconductivity. In this presentation, we will discuss the systematic mechanism to induce superconductivity in Fe-chalcogenide compounds.

  4. Prenatal music exposure induces long-term neural effects.

    PubMed

    Partanen, Eino; Kujala, Teija; Tervaniemi, Mari; Huotilainen, Minna

    2013-01-01

    We investigated the neural correlates induced by prenatal exposure to melodies using brains' event-related potentials (ERPs). During the last trimester of pregnancy, the mothers in the learning group played the 'Twinkle twinkle little star'-melody 5 times per week. After birth and again at the age of 4 months, we played the infants a modified melody in which some of the notes were changed while ERPs to unchanged and changed notes were recorded. The ERPs were also recorded from a control group, who received no prenatal stimulation. Both at birth and at the age of 4 months, infants in the learning group had stronger ERPs to the unchanged notes than the control group. Furthermore, the ERP amplitudes to the changed and unchanged notes at birth were correlated with the amount of prenatal exposure. Our results show that extensive prenatal exposure to a melody induces neural representations that last for several months.

  5. Prenatal Music Exposure Induces Long-Term Neural Effects

    PubMed Central

    Partanen, Eino; Kujala, Teija; Tervaniemi, Mari; Huotilainen, Minna

    2013-01-01

    We investigated the neural correlates induced by prenatal exposure to melodies using brains' event-related potentials (ERPs). During the last trimester of pregnancy, the mothers in the learning group played the ‘Twinkle twinkle little star’ -melody 5 times per week. After birth and again at the age of 4 months, we played the infants a modified melody in which some of the notes were changed while ERPs to unchanged and changed notes were recorded. The ERPs were also recorded from a control group, who received no prenatal stimulation. Both at birth and at the age of 4 months, infants in the learning group had stronger ERPs to the unchanged notes than the control group. Furthermore, the ERP amplitudes to the changed and unchanged notes at birth were correlated with the amount of prenatal exposure. Our results show that extensive prenatal exposure to a melody induces neural representations that last for several months. PMID:24205353

  6. Ethanol induces rapid lipid peroxidation and activation of nuclear factor-kappa B in cerebral vascular smooth muscle: relation to alcohol-induced brain injury in rats.

    PubMed

    Altura, Burton M; Gebrewold, Asefa; Zhang, Aimin; Altura, Bella T

    2002-06-07

    The present study was designed to test the hypothesis that acute administration of alcohol (ethanol) to primary cultured cerebral vascular smooth muscle cells will cause lipid peroxidation, inhibition of IkappaB phosphorylation, and inhibition of nuclear transcription factor-kappa B (NF-kappaB). Ethanol (10, 25, 100 mM) resulted in concentration-dependent rises in malondialdehyde in as little as 30-45 min after exposure to the alcohol, rising to levels 2.5-10x normal after 18-24 h. Using EMSA assays and specific antibodies, ethanol caused three DNA-binding proteins (p50, p65, c-Rel) to rise in nuclear extracts in a concentration-dependent manner. Using a rabbit antibody, IkappaB phosphorylation (and degradation) was stimulated by ethanol (in a concentration-dependent manner) and inhibited by a low concentration of the NF-kappaB inhibitor, pyrrolidine dithiocarbamate. These new biochemical and molecular data indicate that ethanol, even in physiologic concentrations, can elicit rapid lipid peroxidation and activation of NF-kappaB in cerebral vascular muscle cells. The present results when viewed in light of other recently published data suggest that ethanol-induced lipid peroxidation and activation of nuclear transcription factors probably play important roles in alcohol-induced brain-vascular damage, neurobehavioral actions and stroke.

  7. Exacerbation of Alcohol-Induced Oxidative Stress in Rats by Polyunsaturated Fatty Acids and Iron Load

    PubMed Central

    Patere, S. N.; Majumdar, A. S.; Saraf, M. N.

    2011-01-01

    The hypothesis that excessive intake of vegetable oil containing polyunsaturated fatty acids and iron load precipitate alcohol-induced liver damage was investigated in a rat model. In order to elucidate the mechanism underlying this synergism, the serum levels of iron, total protein, serum glutamate pyruvate transaminase, liver thiobarbituric acid reactive substances, and activities of antioxidant enzymes superoxide dismutase, catalase in liver of rats treated with alcohol, polyunsaturated fatty acids and iron per se and in combination were examined. Alcohol was fed to the rats at a level of 10-30% (blood alcohol was maintained between 150-350 mg/dl by using head space gas chromatography), polyunsaturated fatty acids at a level of 15% of diet and carbonyl iron 1.5-2% of diet per se and in combination to different groups for 30 days. Hepatotoxicity was assessed by measuring serum glutamate pyruvate transaminase, which was elevated and serum total protein, which was decreased significantly in rats fed with a combination of alcohol, polyunsaturated fatty acids and iron. It was also associated with increased lipid peroxidation and disruption of antioxidant defense in combination fed rats as compared to rats fed with alcohol or polyunsaturated fatty acids or iron. The present study revealed significant exacerbation of the alcohol-induced oxidative stress in presence of polyunsaturated fatty acids and iron. PMID:22303057

  8. A Smarter Pathway for Delivering Cue Exposure Therapy? The Design and Development of a Smartphone App Targeting Alcohol Use Disorder

    PubMed Central

    Stenager, Elsebeth; Nielsen, Bent; Nielsen, Anette Søgaard; Yu, Fei

    2017-01-01

    Background Although the number of alcohol-related treatments in app stores is proliferating, none of them are based on a psychological framework and supported by empirical evidence. Cue exposure treatment (CET) with urge-specific coping skills (USCS) is often used in Danish treatment settings. It is an evidence-based psychological approach that focuses on promoting “confrontation with alcohol cues” as a means of reducing urges and the likelihood of relapse. Objective The objective of this study was to describe the design and development of a CET-based smartphone app; an innovative delivery pathway for treating alcohol use disorder (AUD). Methods The treatment is based on Monty and coworkers’ manual for CET with USCS (2002). It was created by a multidisciplinary team of psychiatrists, psychologists, programmers, and graphic designers as well as patients with AUD. A database was developed for the purpose of registering and monitoring training activities. A final version of the CET app and database was developed after several user tests. Results The final version of the CET app includes an introduction, 4 sessions featuring USCS, 8 alcohol exposure videos promoting the use of one of the USCS, and a results component providing an overview of training activities and potential progress. Real-time urges are measured before, during, and after exposure to alcohol cues and are registered in the app together with other training activity variables. Data packages are continuously sent in encrypted form to an external database and will be merged with other data (in an internal database) in the future. Conclusions The CET smartphone app is currently being tested at a large-scale, randomized controlled trial with the aim of clarifying whether it can be classified as an evidence-based treatment solution. The app has the potential to augment the reach of psychological treatment for AUD. PMID:28137701

  9. [Evaluation of rounded atelectasis induced by exposure to asbestos].

    PubMed

    Kishimoto, Takumi; Gemba, Kenichi; Fujimoto, Nobukazu; Nishi, Hideyuki; Ozaki, Shinji

    2008-09-01

    We encountered 19 patients of rounded atelectasis induced by exposure to asbestos from 2000 to 2007. All patients were men whose ages arranged from 60 to 89 years with a mean of 74.2 years. Twenty rounded atelectasis were present in the right lung and 5 in the left lung. Five patients had 2 rounded atelectasis. In 21 rounded atelectasis were found in Segment 10 and while other 2 found in S1 and each in S5 and 9. Eleven patients were diagnosed with no symptoms through medical examinations. Other 8 patients complained of dyspnea, chest pain and cough. Thirteen patients complicated with benign asbestos pleurisy and only 3 patients accompanied asbestosis. Eighteen patients (95%) displayed pleural plaques and 15 patients with calcified plaques. Ten patients had been exposed to asbestos in the shipyards and 4 in construction works and other 5 patients had also exposed by occupational exposure to asbestos. The mean period of exposure to asbestos was 26.6 years and the mean latency periods from the first asbestos exposure to the diagnosis of rounded atelectasis were 51.6 years. An autopsied patient had 18,100 asbestos bodies per 1 g of dry lung tissue which meant the heavy asbestos exposure. High incidence of pleural plaques and long period of latency from the first exposure to the appearance of rounded atelectasis in this study suggested that rounded atelectasis might appear less high-dose exposure to asbestos than former patients who were reported 6 years ago.

  10. Experimental methods for testing the effects of neurotrophic peptide, ADNF-9, against alcohol-induced apoptosis during pregnancy in c57bl/6 mice.

    PubMed

    Sari, Youssef

    2013-04-24

    Experimental designs for investigating the effects of prenatal alcohol exposure during early embryonic stages in fetal brain growth are challenging. This is mostly due to the difficulty of microdissection of fetal brains and their sectioning for determination of apoptotic cells caused by prenatal exposure to alcohol. The experiments described here provide visualized techniques from mice breeding to the identification of cell death in fetal brain tissue. This study used C57BL/6 mice as the animal model for studying fetal alcohol exposure and the role of trophic peptide against alcohol-induced apoptosis. The breeding consists of a 2-hr matting window to determine the exact stage of embryonic age. An established fetal alcohol exposure model has been used in this study to determine the effects of prenatal alcohol exposure in fetal brains. This involves free access to alcohol or pair-fed liquid diets as the sole source of nutrients for the pregnant mice. The techniques involving dissection of fetuses and microdissection of fetal brains are described carefully, since the latter can be challenging. Microdissection requires a stereomicroscope and ultra-fine forceps. Step-by-step procedures for dissecting the fetal brains are provided visually. The fetal brains are dissected from the base of the primordium olfactory bulb to the base of the metencephalon. For investigating apoptosis, fetal brains are first embedded in gelatin using a peel-away mold to facilitate their sectioning with a vibratome apparatus. Fetal brains embedded and fixed in paraformaldehyde are easily sectioned, and the free floating sections can be mounted in superfrost plus slides for determination of apoptosis or cell death. TUNEL (TdT-mediated dUTP Nick End Labeling; TdT: terminal deoxynucleotidyl transferase) assay has been used to identify cell death or apoptotic cells. It is noteworthy that apoptosis and cell-mediated cytotoxicity are characterized by DNA fragmentation. Thus, the visualized TUNEL

  11. Neonatal screening for prenatal alcohol exposure: assessment of voluntary maternal participation in an open meconium screening program.

    PubMed

    Zelner, Irene; Shor, Sarit; Lynn, Hazel; Roukema, Henry; Lum, Lisa; Eisinga, Kirsten; Koren, Gideon

    2012-05-01

    Meconium fatty acid ethyl esters (FAEEs) are validated biomarkers of fetal alcohol exposure. Meconium FAEE testing can potentially be used as a screen by health-care professionals to identify neonates at-risk for Fetal Alcohol Spectrum Disorder, thereby permitting diagnostic follow-up of these children and early intervention in those who develop disabilities. The purpose of this study was to assess whether women would willingly partake in a screening program of this nature. This was determined by launching a pilot screening program for prenatal alcohol exposure in a high-risk obstetric unit previously shown to have a high prevalence of FAEE-positive meconium via anonymous meconium testing. The program involved voluntary testing of meconium for FAEEs and long-term developmental follow-up of positive cases through an existing public health program. The participation rate in the screening program was significantly lower than when testing was conducted anonymously (78% vs. 95%, respectively; p < 0.05), and the positivity rate was 3% in contrast to 30% observed under anonymous conditions (p < 0.001). These low rates suggest that the majority of mothers who consumed alcohol in pregnancy refused to participate. We conclude that despite the potential benefits of such screening programs, maternal unwillingness to consent, likely due to fear, embarrassment, and guilt, may limit the effectiveness of meconium testing for population-based open screening, highlighting the need for public education and social marketing efforts for such programs to be of benefit.

  12. Alcohol-induced headaches: Evidence for a central mechanism?

    PubMed Central

    Panconesi, Alessandro

    2016-01-01

    Alcoholic drinks (ADs) have been reported as a migraine trigger in about one-third of the migraine patients in retrospective studies. Some studies found that ADs trigger also other primary headaches. The studies concerning the role of ADs in triggering various types of primary headaches published after the International Headache Society classification criteria of 1988 were reviewed, and the pathophysiological mechanisms were discussed. Many studies show that ADs are a trigger of migraine without aura (MO), migraine with aura (MA), cluster headache (CH), and tension-type headache (TH). While data on MO and CH are well delineated, those in MA and TH are discordant. There are sparse reports that ADs are also triggers of less frequent types of primary headache such as familial hemiplegic migraine, hemicrania continua, and paroxysmal hemicrania. However, in some countries, the occurrence of alcohol as headache trigger is negligible, perhaps determined by alcohol habits. The frequency estimates vary widely based on the study approach and population. In fact, prospective studies report a limited importance of ADs as migraine trigger. If ADs are capable of triggering practically all primary headaches, they should act at a common pathogenetic level. The mechanisms of alcohol-provoking headache were discussed in relationship to the principal pathogenetic theories of primary headaches. The conclusion was that vasodilatation is hardly compatible with ADs trigger activity of all primary headaches and a common pathogenetic mechanism at cortical, or more likely at subcortical/brainstem, level is more plausible. PMID:27114660

  13. Development and Optimization of a Novel Prolonged Release Formulation to Resist Alcohol-Induced Dose Dumping.

    PubMed

    Gujjar, Chaitanya Yogananda; Rallabandi, Balaramesha Chary; Gannu, Ramesh; Deulkar, Vallabh Subashrao

    2016-04-01

    Alcohol-induced dose dumping is a serious concern for the orally administered prolonged release dosage forms. The study was designed to optimize the independent variables, propylene glycol alginate (PGA), Eudragit RS PO (ERS) and coating in mucoadhesive quetiapine prolonged release tablets 200 mg required for preventing the alcohol-induced dose dumping. Optimal design based on response surface methodology was employed for the optimization of the composition. The formulations are evaluated for in vitro drug release in hydrochloric acid alone and with 40% v/v ethanol. The responses, dissolution at 120 min without alcohol (R1) and dissolution at 120 min with alcohol (R2), were statistically evaluated and regression equations are generated. PGA as a hydrophilic polymeric matrix was dumping the dose when dissolutions are carried in 0.1 N hydrochloric acid containing 40% v/v ethanol. ERS addition was giving structural support to the swelling and gelling property of PGA, and thus, was reducing the PGA erosion in dissolution media containing ethanol. Among the formulations, four formulations with diverse composition were meeting the target dissolution (30-40%) in both the conditions. The statistical validity of the mathematical equations was established, and the optimum concentration of the factors was established. Validation of the study with six confirmatory runs indicated high degree of prognostic ability of response surface methodology. Further coating with ReadiLycoat was providing an additional resistance to the alcohol-induced dose dumping. Optimized compositions showed resistance to dose dumping in the presence of alcohol.

  14. Isopropyl alcohol intoxication in a neonate through chronic dermal exposure: a complication of a culturally-based umbilical care practice.

    PubMed

    Vivier, P M; Lewander, W J; Martin, H F; Linakis, J G

    1994-04-01

    A 21-day-old boy presented to our emergency department hypotonic, lethargic, and intermittently unresponsive to pain. A workup for ketoacidosis, sepsis, and central nervous system hemorrhage was negative. A urine drug screen collected eight hours after hospitalization showed 39 mg/dl of isopropyl alcohol and 76 mg/dl of acetone. The first serum drug analysis was not performed until 18 hours after admission, at a time when there had been clinical improvement. The isopropyl alcohol concentration was 8 mg/dl, and the acetone concentration was 203 mg/dl. Management was supportive, and the patient stabilized. He was discharged from the hospital in good health in three days. A further review of the history showed no evidence for an oral exposure to isopropyl alcohol. However, since leaving the maternity hospital the mother had been applying gauze pads or cotton balls soaked with isopropyl alcohol to the umbilicus with every diaper change. We conclude that the child suffered from an isopropyl alcohol intoxication that occurred by absorption through the umbilical area.

  15. Overexpression of serum response factor in astrocytes improves neuronal plasticity in a model of early alcohol exposure.

    PubMed

    Paul, A P; Medina, A E

    2012-09-27

    Neuronal plasticity deficits underlie many of the cognitive problems seen in fetal alcohol spectrum disorders (FASD). We have developed a ferret model showing that early alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. Recently, we showed that this deficit could be reversed by overexpression of serum response factor (SRF) in the primary visual cortex during the period of monocular deprivation (MD). Surprisingly, this restoration was observed throughout the extent of visual cortex and most of the cells transfected by the virus were positive for the astrocytic marker GFAP rather than the neuronal marker NeuN. Here we test whether overexpression of SRF exclusively in astrocytes is sufficient to restore OD plasticity in alcohol-exposed ferrets. To accomplish that, first we exposed cultured astrocytes to Sindbis viruses carrying either a constitutively active form of SRF (SRF+), a dominant negative (SRF-) or control Green Fluorescent Protein (GFP). After 24h, these astrocytes were implanted in the visual cortex of alcohol-exposed animals or saline controls one day before MD. Optical imaging of intrinsic signals showed that alcohol-exposed animals that were implanted with astrocytes expressing SRF, but not SRF- or GFP, showed robust restoration of OD plasticity in all visual cortex. These findings suggest that overexpression of SRF exclusively in astrocytes can improve neuronal plasticity in FASD.

  16. Ethylglucuronide in maternal hair as a biomarker of prenatal alcohol exposure.

    PubMed

    Gutierrez, Hilda L; Hund, Lauren; Shrestha, Shikhar; Rayburn, William F; Leeman, Lawrence; Savage, Daniel D; Bakhireva, Ludmila N

    2015-09-01

    While direct ethanol metabolites, including ethylglucuronide (EtG), play an important role for the confirmation of prenatal alcohol exposure (PAE), their utility is often limited by their short half-lives in blood and urine. Maternal hair allows for a retrospective measure of PAE for up to several months. This study examined the validity of hair EtG (hEtG) relative to self-reporting and five other biomarkers in 85 pregnant women. Patients were recruited from a UNM prenatal clinic, which provides care to women with substance abuse and addiction disorders. The composite index, which was based on self-reported measures of alcohol use and allowed us to classify subjects into PAE (n = 42) and control (n = 43) groups, was the criterion measure used to estimate the sensitivity and specificity of hEtG. Proximal segments of hair were collected at enrollment (average 22.0 gestational weeks) and analyzed by LC-MS/MS. At the same visit, maternal blood and urine specimens were collected for analysis of GGT, %dCDT, PEth, uEtG, and uEtS. The study population included mostly opioid-dependent (80%) patients, a large proportion of ethnic minorities (75.3% Hispanic/Latina, 8.2% American Indian, 4.7% African-American), and patients with low education (48.2% < high school). The mean maternal age at enrollment was 26.7 ± 4.8 years. Hair EtG demonstrated 19% sensitivity and 86% specificity. The sensitivities of other biomarkers were comparable (5-20%) to hEtG but specificities were higher (98-100%). Hair EtG sensitivity improved when combined with other biomarkers, especially with GGT (32.5%) and PEth (27.5%). In addition, validity of hEtG improved in patients with less frequent shampooing and those who did not use hair dyes/chemical treatments. These data suggest that hEtG alone is not a sufficiently sensitive or specific biomarker to be used separately for the identification of PAE, but might be useful in a battery along with other maternal biomarkers.

  17. Alcohol-induced suppression of KDM6B dysregulates the mineralization potential in dental pulp stem cells.

    PubMed

    Hoang, Michael; Kim, Jeffrey J; Kim, Yiyoung; Tong, Elizabeth; Trammell, Benjamin; Liu, Yao; Shi, Songtao; Lee, Chang-Ryul; Hong, Christine; Wang, Cun-Yu; Kim, Yong

    2016-07-01

    Epigenetic changes, such as alteration of DNA methylation patterns, have been proposed as a molecular mechanism underlying the effect of alcohol on the maintenance of adult stem cells. We have performed genome-wide gene expression microarray and DNA methylome analysis to identify molecular alterations via DNA methylation changes associated with exposure of human dental pulp stem cells (DPSCs) to ethanol (EtOH). By combined analysis of the gene expression and DNA methylation, we have found a significant number of genes that are potentially regulated by EtOH-induced DNA methylation. As a focused approach, we have also performed a pathway-focused RT-PCR array analysis to examine potential molecular effects of EtOH on genes involved in epigenetic chromatin modification enzymes, fibroblastic markers, and stress and toxicity pathways in DPSCs. We have identified and verified that lysine specific demethylase 6B (KDM6B) was significantly dysregulated in DPSCs upon EtOH exposure. EtOH treatment during odontogenic/osteogenic differentiation of DPSCs suppressed the induction of KDM6B with alterations in the expression of differentiation markers. Knockdown of KDM6B resulted in a marked decrease in mineralization from implanted DPSCs in vivo. Furthermore, an ectopic expression of KDM6B in EtOH-treated DPSCs restored the expression of differentiation-related genes. Our study has demonstrated that EtOH-induced inhibition of KDM6B plays a role in the dysregulation of odontogenic/osteogenic differentiation in the DPSC model. This suggests a potential molecular mechanism for cellular insults of heavy alcohol consumption that can lead to decreased mineral deposition potentially associated with abnormalities in dental development and also osteopenia/osteoporosis, hallmark features of fetal alcohol spectrum disorders.

  18. Establishment of the South-Eastern Norway Regional Health Authority Resource Center for Children with Prenatal Alcohol/Drug Exposure

    PubMed Central

    Løhaugen, Gro C. C.; Flak, Marianne Møretrø; Gerstner, Thorsten; Sundberg, Cato; Lerdal, Bjørn; Skranes, Jon

    2015-01-01

    This paper presents a new initiative in the South-Eastern Health Region of Norway to establish a regional resource center focusing on services for children and adolescents aged 2–18 years with prenatal exposure to alcohol or other drugs. In Norway, the prevalence of fetal alcohol spectrum (FAS) is not known but has been estimated to be between 1 and 2 children per 1000 births, while the prevalence of prenatal exposure to illicit drugs is unknown. The resource center is the first of its kind in Scandinavia and will have three main objectives: (1) provide hospital staff, community health and child welfare personnel, and special educators with information, educational courses, and seminars focused on the identification, diagnosis, and treatment of children with a history of prenatal alcohol