Aims

To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.

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Wednesday, August 7, 2013

Conference - New Directions in the Study of Alcohol Group 2013

                                                                                                                                                     LOCATION                                                                                                                       
Birmingham
                                                                                                                  
EVENT THEME                                                                                                                       
Alcohol Policy

EVENT SUMMARY
New Directions in the Study of Alcohol Group has provided a safe environment where alcohol practitioners, researchers, service managers and commissioners have explored and debated contemporary challenges in the field since the mid 1970.

 2013 conference reviews the development of alcohol related work with families including some of the leading researchers internationally: Professor Jim Orford; Professor Alex Copello and Professor Richard Velleman. > > > >  Read More

News Release - NIH Study Explains Neuroscience of Habit Breaking




Recent research from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) sheds new light on habitual behaviors, specifically the circuits in the brain that allow mice to break from routine actions. Such shifting between old habits and new behavior aimed at accomplishing a particular goal are critical to flexible decision-making in everyday life. It also has important implications for mental health and substance abuse interventions. The inability to shift between routine behavior and new goal-directed actions may underlie disorders such as addiction and obsessive compulsive disorder.  > > > >    Read More

Adenosine signaling in striatal circuits and alcohol use disorders





Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors.

Moreover, decreased A2AR function is associated with decreased CREB activity in the DMS, which enhances goal-oriented behaviors and contributes to excessive ethanol drinking in mice. Interestingly, caffeine, the most commonly used psychoactive substance, is known to inhibit both the A1R and A2AR. This dampened adenosine receptor function may mask some of the acute intoxicating effects of ethanol.

Furthermore, based on the fact that A2AR activity plays a role in goal-directed behavior, caffeine may also promote ethanol-seeking behavior. The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, which may be responsible for the regulation of inhibitory behavioral control over drug rewarding processes through the indirect pathway of the basal ganglia circuit.

Furthermore, the antagonistic interactions between adenosine and dopamine receptors in the striatum also play an integral role in alcoholism and addiction-related disorders.

This review focuses on regulation of adenosine signaling in striatal circuits and the possible implication of caffeine in goal-directed behaviors and addiction.



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Request Rerprin E-Mail:   choids@mayo.edu    

Tuesday, August 6, 2013

Deletion of Prkcz Increases Intermittent Ethanol Consumption in Mice




Prkcz has been identified as a gene whose expression is positively correlated with ethanol (EtOH) consumption in mice and is also induced by EtOH. Two proteins are produced from Prkcz: protein kinase M zeta (PKMζ), which is expressed in the nervous system and protein kinase C zeta (PKCζ), which is expressed in other tissues. We examined Prkcz−/− mice that lack PKCζ and PKMζ to investigate the role of this gene in behavioral responses to EtOH.
 
Male Prkcz−/− and wild-type littermates were tested for EtOH consumption using 4 procedures: 24-hour intermittent access, 4-hour limited intermittent access, 4-day drinking-in-the-dark, and 24-hour continuous access. We also assessed the acute hypnotic effect of EtOH, EtOH reward, and taste preference for sweet-, bitter-, salty-, and umami-flavored solutions. Finally, we determined whether EtOH could increase PKMζ and PKCζ transcripts and protein expression in wild-type mice using quantitative PCR and Western blot analysis.
 
Prkcz−/− mice consumed more EtOH than their wild-type littermates in both intermittent access procedures, but not in the drinking-in-the-dark or 24-hour continuous access procedures. EtOH exposure increased Prkcz transcripts in cultured PC12 cells, and intermittent EtOH consumption increased PKMζ protein in the ventral striatum of wild-type mice.
 
Absence of PKMζ in the brain is associated with increased EtOH intake during procedures that incorporate intermittent consumption sessions every other day. Our data suggest that EtOH induces PKMζ, which acts in a negative feedback loop to limit binge-like EtOH.



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Request Reprint E-Mail:    romessing@austin.utexas.edu

Female Rats Display Enhanced Rewarding Effects of Ethanol That Are Hormone Dependent




Ethanol (EtOH) abuse is a major health and economic concern, particularly for females who appear to be more sensitive to the rewarding effects of EtOH. This study compared sex differences to the rewarding and aversive effects of EtOH using place-conditioning procedures in rats.
 
Separate groups of adult (male, female, ovariectomized [OVX] female) and adolescent (male and female) rats received EtOH (0, 0.5, 1.0, 2.0, or 2.5 g/kg, intraperitoneal) and were confined to their initially nonpreferred side of our conditioning apparatus for 30 minutes. On alternate days, they received saline and were confined to the other side. Following 5 drug pairings, the rats were retested for preference behavior. Separate cohorts of the same groups of rats were injected with a similar dose range of EtOH, and blood EtOH levels (BELs) were compared 30 minutes later.
 
EtOH produced rewarding or aversive effects in a dose-dependent manner. An intermediate dose of EtOH (1.0 g/kg) produced rewarding effects in adult female, but not in male or OVX female rats, suggesting that ovarian hormones facilitate the rewarding effects of EtOH. Similarly, this intermediate dose of EtOH produced rewarding effects in adolescent female, but not in male rats. The highest dose of EtOH (2.5 g/kg) produced aversive effects that were similar across all adult groups. However, the aversive effects of EtOH were lower in adolescents than adults, suggesting that adolescents are less sensitive to the aversive effects of EtOH. The aversive effects of EtOH did not vary across the estrous cycle in intact adult females. There were also no group differences in BELs, suggesting that our results are not related to EtOH metabolism.
 
Our results in rats suggest that human females may be more vulnerable to EtOH abuse due to enhanced rewarding effects of this drug that are mediated by the presence of ovarian hormones.


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Request Reprint E-Mail:     lodell@utep.edu

he Association of Mild, Moderate, and Binge Prenatal Alcohol Exposure and Child Neuropsychological Outcomes: A Meta-Analysis




The objective of this review is to evaluate the literature on the association between mild, moderate, and binge prenatal alcohol exposure and child neurodevelopment.
 
Meta-analysis with systematic searches of MEDLINE (1970 through August 2012), EMBASE (1988 through August 2012), and PsycINFO® (1970 through August 2012) and examination of selected references.

From 1,593 articles, we identified 34 presenting data from cohort studies that met our inclusion criteria. Information on study population, outcomes, measurement instruments, timing and quantification of alcohol exposure, covariates, and results was abstracted. Outcomes included academic performance, attention, behavior, cognition, language skills, memory, and visual and motor development. The quality of each article was assessed by 2 researchers using the Newcastle–Ottawa Scale. Based on 8 studies of 10,000 children aged 6 months through 14 years, we observed a significant detrimental association between any binge prenatal alcohol exposure and child cognition (Cohen's d [a standardized mean difference score] −0.13; 95% confidence interval [CI], −0.21, −0.05). Based on 3 high-quality studies of 11,900 children aged 9 months to 5 years, we observed a statistically significant detrimental association between moderate prenatal alcohol exposure and child behavior (Cohen's d −0.15; 95% CI, −0.28, −0.03). We observed a significant, albeit small, positive association between mild-to-moderate prenatal alcohol exposure and child cognition (Cohen's d 0.04; 95% CI, 0.00, 0.08), but the association was not significant after post hoc exclusion of 1 large study that assessed mild consumption nor was it significant when including only studies that assessed moderate alcohol consumption. None of the other completed meta-analyses resulted in statistically significant associations between mild, moderate, or binge prenatal alcohol exposure and child neuropsychological outcomes.
 
Our findings support previous findings suggesting the detrimental effects of prenatal binge drinking on child cognition. Prenatal alcohol exposure at levels less than daily drinking might be detrimentally associated with child behavior. The results of this review highlight the importance of abstaining from binge drinking during pregnancy and provide evidence that there is no known safe amount of alcohol to consume while pregnant.


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Request Reprint E-Mail:    aflak@emory.edu

Monday, August 5, 2013

Alcohol News - 31/2013


 


 
The Local (Norway) - Norway risks even higher booze taxes

Norway is considering imposing even higher taxes on alcoholic drinks, a move that would bring it within a whisker of becoming world's most expensive place for a tipple.Read more

The Foreigner (Norway) - Norway government alcohol monopoly eyes tax free

Vinmonopolet is considering moving into the airport alcohol business as drink sales figures decline.


Finland Times (Finland) - No tax hike on alcohol in budget likely

The government is likely not to increase tax on alcohol in the upcoming budget for the year 2014 as the tax hike might increase the import of the alcoholic products from the neighbouring countries of Russia and Estonia by the travellers.


THL (Finland) - Pekka Puska: Health should be prioritized over business interests

Pekka Puska’s speech at the Savonlinna Opera Festival public meeting on 30 July, 2013. The World Health Organization WHO held a major international conference in Helsinki in June. In the summit, the WHO appealed to world decision makers to put health in focus in all policy making.


WalesOnline (Wales) - Wales could go it alone over cigarette packaging and minimum alcohol pricing, says health minister

Health Minister Mark Drakeford has revealed he is giving serious consideration as to whether Wales could go it alone on major public health issues such as plain cigarette packaging and a minimum price for alcohol.


Globe and Mail (Canada) - Mothers Against Drunk Driving take aim at Tory plan for alcohol in Nova Scotia corner stores

The CEO of Mothers Against Drunk Driving says Nova Scotia’s opposition Progressive Conservatives have engaged in “dirty politics” by suggesting the group supports the party’s proposal to introduce the sale of beer and wine in corner stores.


The Guardian (UK) - Channel 4 rapped for airing alcohol ads when kids were likely to be watching

Channel 4 has been rapped on the knuckles for running alcohol ads during shows likely to appeal to children, including hit US comedy import The Big Bang Theory.


StatesChronicle - New Studys Suggests Relation Between Brain Hyderactivity to Alcohol Consumption

A new study conducted in Canada by McGill University’s Professor Marco Leyton from the Department of Psychiatry can help in diagnosing and treating patients undergoing treatment caused by alcoholism.


The Daily Progress (USA) - Gifts to ABC from alcohol industry a 'gray area'

State Alcoholic Beverage Control employees reported more than $50,000 in gifts and entertainment from 2008 to 2011, primarily to pay for conference trips but also including tickets to car races, comedy shows and a Washington Redskins game as well as "spa service."


Health-e (South Africa) - Govt moves to stop alcohol ads

South Africans like to drink. In fact, according to the World Health Organisation (WHO), we are some of the biggest drinkers in the world. But, alcohol kills around 130 South Africans every day and well over half of all road accidents are caused by drunk drivers.


IrishCentral (Ireland) - Alcohol fuels many of Ireland’s fatal assaults research finds

Deputy State Pathologist Michael Curtis has found that alcohol is a major factor when it comes to the cause of violent crimes in Ireland.


EurekAlert (USA) - Fewer states holding alcohol retailers responsible for harms from illegal service

Fewer states are holding alcohol retailers liable for harms caused by customers who were served illegally, according to a new report from researchers at Alcohol Policy Consultations and the Center on Alcohol Marketing and Youth (CAMY) at the Johns Hopkins Bloomberg School of Public Health.


Independent Online (South Africa) - ‘We’ll fight alcohol with bare knuckles’

South Africans like to drink. In fact, according to the World Health Organisation, we are some of the biggest drinkers in the world. But, alcohol kills around 130 South Africans every day and well over half of all road accidents are caused by drunk drivers.


Bury Times (UK) - Hospitals seeing large numbers of drunk children in A&E departments

ALMOST one in seven people admitted to local accident and emergency departments with alcohol problems are children, new figures have revealed.


FRANCE 24 (France) - 'Le binge drinking' on the rise in France

France on Sunday officially replaced the English term “binge drinking” with the French alternative “beuverie express”, a move that may reflect how drinking habits in the country have changed in recent years.


TIME (France) - France Finally Finds the Right Words to Describe Binge Drinking

The French Ministry of Culture and Communication, better known as the language police, added a decidedly un-French term to its approved lexicon on Sunday. From now on, chugging alcohol with the sole motive of getting smashed is no longer “le binge drinking” — it’s la beuverie express (literally, fast drinking).


FASD News - 30/2013






 
NEWS and ARTICLES

SBS (Australia) - Foetal alcohol syndrome victim calls on pregnant women not to drink

When it comes to the dangers of drinking alcohol while pregnant, the message may not be getting through. Australian researchers say only two out of three women know that alcohol can affect their unborn child.


Parent Herald - Alcohol During Pregnancy Damages Learning and Memory in Children, Study Finds

A team of researchers from Xinxiang Medical University in China found that maternal alcohol consumption during pregnancy damaged learning and memory in children.


Voice of America (South Africa) - Mentally Disabled Women Endure Intense Abuse in South Africa

They’re mentally ill or disabled, suffering from conditions such as cerebral palsy and fetal alcohol syndrome. The women are at Ikhaya Loxolo, “Home of Peace,” a collection of mud huts in the district of Hobeni in a particularly isolated part of South Africa’s Eastern Cape province.


EurekAlert - FASD impacts brain development throughout childhood and adolescence not just at birth

Medical researchers at the University of Alberta recently published findings showing that brain development is delayed throughout childhood and adolescence for people born with Fetal Alcohol Spectrum Disorder (FASD).


Alaska Dispatch (Canada) - Senior Nunavut judge urges territory to help inmates with FASD

An offender suffering from Fetal Alcohol Spectrum Disorder (FASD) will have a hard time getting treatment in Canada’s eastern Arctic territory of Nunavut because there are no programs for the disorder in the territory’s correctional system.


The Guardian (UK) - A day in the life of ... a health charity executive director

Our charity, the National Organisation for Foetal Alcohol Syndrome, supports people who have foetal alcohol-related disabilities as well as their families, and I'm a pretty hands-on type of person so no two days are the same.


Ninemsn (Australia) - GPs fail to warn drinking mums, prof says

GPs have been too concerned about offending people to warn women of the dangers of drinking while pregnant, leaving their unborn children at risk of birth defects, a professor of pediatrics says.


Scotland on Sunday (Scotland) - Alcohol syndrome babies slip through safety net

LARGE numbers of children in Scotland affected by their mothers drinking alcohol during pregnancy have not been diagnosed, experts suspect.


National Magazine (Canada) - Court system an abusive one for victims of FASD

The criminal justice system can be an abusive one for children and adults with the kind of disability that robs them the ability to foresee the consequences of their actions, says a lawyer who is intimately acquainted with the problem.


Labcanada (Canada) - $1.7M project examines genetic roots of FASD

The Canadian Institutes of Health Research has awarded $1.37 million in funding to a team at the University of Manitoba that is led by James Davie, Canada Research Chair (CRC) in Chromatin Dynamics.




UPCOMING EVENTS

First International Conference on Prevention of FASD

This is the first international conference to address the primary, secondary and tertiary prevention of FASD. Plenary sessions will promote discussion and reflection on promising and innovative approaches for preventing FASD, such as policies and programs to address alcohol use and the social determinants of health.


MOFAS - 2013 FASD matters conference: exploring the spectrum November 14-15, 2013

The Minnesota Organization on Fetal Alcohol Syndrome (MOFAS) is the statewide organization serving as the leading voice and resource on Fetal Alcohol Spectrum Disorder (FASD) in Minnesota – standing up for the rights of the FASD community, providing education and training so FASD is better understood and working to ensure that all women know that there is no safe level of alcohol use during pregnancy.


Living With FASD 2013 Summit, September 9 2013

The purpose of this telesummit is to provide families with information about practical strategies to implement at home, based on the newest FASD research. Speakers have been specially selected because they have experience on a professional level and also have first-hand experience raising children with FASD.


Interprofessional Continuing Education - 6th National Biennial Conference on Adolescence and adults with Fetal Alcohol Spectrum Disorders - Call for Abstracts

he conference does not cover honoraria, accommodation, travel or other associated expenses. However, the primary presenter of 3-hour/90-minute abstracts willreceive complimentary registration to the conference (~$600 value).




VIDEOS, MATERIALS

Youtube - FASD COMMUNITIES, informational video by Elizabeth H.

Many young adults grow up with FASD and have problems adjusting to life after school. FASD Communities is a 501c(3) organization that raises funds to establish group homes for this growing population of young adults.


sydney.edu.au - A success story - a community led collaboration with remote indigenous Australia

‘Our children are our greatest asset’ says Professor Elizabeth Elliott, paediatrician at the Sydney Children’s Hospitals Network, Westmead, and Professor of Paediatrics and Child Health at the University of Sydney. Yet many children suffer brain damage even before they are born, through exposure to alcohol in the womb.




RESEARCH

PubMed - Involving consumers and the community in the development of a diagnostic instrument for fetal alcohol spectrum disorders in Australia

The successful involvement of consumers and the community in the FASD Project can be attributed to active consumer and community participation, which included continued involvement throughout the project, funding of participation activities, and an understanding of the various contributions by the Collaboration members.


Educational Psychology in Practice - Foetal Alcohol Spectrum Disorders: as prevalent as autism?

An examination of the literature on Foetal Alcohol Spectrum Disorders (FASD) and its relevance to the work of Educational Psychologists (EPs) suggested that the impact of FASD on EPs’ casework is an area which has been underexplored, and which merits further attention.


Brain Sciences - Drug-Induced Apoptosis: Mechanism by which Alcohol and Many Other Drugs Can Disrupt Brain Development

Maternal ingestion of alcohol during pregnancy can cause a disability syndrome termed Fetal Alcohol Spectrum Disorder (FASD), which may include craniofacial malformations, structural pathology in the brain, and a variety of long-term neuropsychiatric disturbances.


Alcoholism - Early Fetal Binge Alcohol Exposure Predicts High Behavioral Symptom Scores in 5.5-Year-Old Children

Fetal binge alcohol exposure has been associated with neurobehavioral and cognitive symptoms. This study explored whether binge drinking mainly before recognition of pregnancy predicted high symptom scores on the Strengths and Difficulties Questionnaire (SDQ) in 5.5-year-old children.


Alcohol - Neonatal ethanol exposure results in dose-dependent impairments in the acquisition and timing of the conditioned eyeblink response and altered cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats

Exposure to ethanol in neonatal rats results in reduced neuronal numbers in the cerebellar cortex and deep nuclei of juvenile and adult animals. This reduction in cell numbers is correlated with impaired delay eyeblink conditioning (EBC), a simple motor learning task in which a neutral conditioned stimulus (CS; tone) is repeatedly paired with a co-terminating unconditioned stimulus (US; periorbital shock).

News Release - New insight on how the brain forms habits


New data offers a glimpse into the neurobiological mechanisms underlying the formation of habitual actions, such as addiction to alcohol.
In a study conducted in mice and rats, scientists in NIAAA’s Laboratory for Integrative Neuroscience examined the cellular basis for learning and memory in the dorsolateral striatum, a part of the brain involved in habit learning. A particular receptor in the dorsolateral striatum, the cannabinoid type 1 receptor (CB1), is critical for habit learning.  > > > >   Read More

Dominance of the Inactive Asian Variant Over Activity and Protein Contents of Mitochondrial Aldehyde Dehydrogenase 2 in Human Liver


It has been well documented that a variant allele of mitochondrial aldehyde dehydrogenase 2 (ALDH2), ALDH2*2, commonly occurs in East Asians but rarely in other ethnic populations. This unique allelic variation significantly influences drinking behavior and susceptibility to development of alcoholism. Previous structural, functional, and cellular studies indicate that the resulting variant polypeptide subunit K (Lys-487) exerts dominance of null activity and shorter half-life over the tetrameric enzyme molecules in distinct manners. However, the in vivo evidence for the proposed dominance mechanisms remains lacking.
 
To address this question, we investigated 33 surgical liver samples identified to be normal homozygous ALDH2*1/*1 (n = 17), heterozygous ALDH2*1/*2 (n = 13), and variant homozygous ALDH2*2/*2 (n = 3). The ALDH2 activity was determined at a sufficient low acetaldehyde concentration (3 μM) and the isozyme protein amount by immunotitration using purified class-specific antibodies.

The tissue ALDH2 activity in heterozygotes was 17% that of the ALDH2*1/*1 genotype (p < 0.001), whereas the activity of ALDH2*2/*2 was too low to be precisely determined. The protein amounts of tissue ALDH2 in variant homozygotes and heterozygotes were similar but only 30 to 40% that of normal homozygotes (p < 0.01). Linear regression analyses show that ALDH2 activities were significantly correlated with the protein contents in normal homozygotes and heterozygotes, respectively (p < 0.005). The specific activity of ALDH2 per enzyme protein in ALDH2*1/*2 was 38% that of ALDH2*1/*1 (p < 0.001).
 
These results are in good agreement with those predicted by the model studies, thus providing in vivo evidence for differential impairments of hepatic acetaldehyde oxidation with alcohol metabolism in individuals carrying ALDH2*1/*2 and ALDH2*2/*2 genotypes.



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Request Reprint E-Mail:    yinsj@ndmc.idv.tw

Selectively Bred Crossed High-Alcohol-Preferring Mice Drink to Intoxication and Develop Functional Tolerance, But Not Locomotor Sensitization During Free-Choice Ethanol Access




Crossed high-alcohol-preferring (cHAP) mice were selectively bred from a cross of the HAP1 × HAP2 replicate lines and demonstrate blood ethanol concentrations (BECs) during free-choice drinking reminiscent of those observed in alcohol-dependent humans. In this report, we investigated the relationship between free-choice drinking, intoxication, tolerance, and sensitization in cHAP mice. We hypothesized that initially mice would become ataxic after drinking alcohol, but that increased drinking over days would be accompanied by increasing tolerance to the ataxic effects of ethanol (EtOH).
 
Male and female cHAP mice had free-choice access to 10% EtOH and water (E), while Water mice (W) had access to water alone. In experiment 1, the first drinking experience was monitored during the dark portion of the cycle. Once E mice reached an average intake rate of ≥1.5 g/kg/h, they, along with W mice, were tested for footslips on a balance beam, and BECs were assessed. In experiments 2, 3, and 4, after varying durations of free-choice 10% EtOH access (0, 3, 14, or 21 days), mice were challenged with 20% EtOH and tested for number of footslips on a balance beam or locomotor stimulant response. Blood was sampled for BEC determination.
 
We found that cHAP mice rapidly acquire alcohol intakes that lead to ataxia. Over time, cHAP mice developed behavioral tolerance to the ataxic effects of alcohol, paralleled by escalating alcohol consumption. However, locomotor sensitization did not develop following 14 days of free-choice EtOH access.

Overall, we observed increases in free-choice drinking with extended alcohol access paralleled by increases in functional tolerance, but not locomotor sensitization. These data support our hypothesis that escalating free-choice drinking over days in cHAP mice is driven by tolerance to alcohol's behavioral effects. These data are the first to demonstrate that escalating free-choice consumption is accompanied by increasing alcohol tolerance. In addition to buttressing the hypothesized importance of tolerance in drinking, our findings suggest that cHAP mice may be a unique, translational resource for studying tolerance as a contributor to and consequence of chronic, excessive EtOH consumption.


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Request Reprint E-Mail:      ngrahame@iupui.edu

Risk of Injury from Drinking: The Difference Which Study Design Makes





The magnitude of risk of injury from drinking, based on emergency department (ED) studies, has been found to vary considerably across studies, and the impact of study design on this variation is unknown.
 
Patients were interviewed regarding drinking within 6 hours prior to the injury or illness event, drinking during the same time the previous week, and usual drinking during the last 30 days. Risk estimates were derived from case–control analysis and from both pair-matched and usual frequency case-crossover analysis.
 
The odds ratio (OR) based on case–control (2.7; 1.9 to 3.8) was larger than that based on pair-matched case-crossover analysis (1.6; 1.0 to 2.6). The control-crossover estimate suggested the case-crossover estimate was an underestimate of risk, and when this adjustment was applied to the case-crossover estimate, risk of injury increased (OR = 3.2; 1.7 to 6.0). Adjusted case-crossover estimates compared with unadjusted showed the largest proportional increase at 7 or more drinks prior to injury (OR = 7.1; 2.2 to 22.9). The case-crossover estimate based on usual frequency of drinking was substantially larger (OR = 10.7; 8.0 to 14.3) than that based on case–control or pair-matched case-crossover analysis, but less than either when adjusted based on control-crossover usual frequency analysis (OR = 2.2; 1.5 to 3.3).
 
The data suggest that while risk of injury based on case–control analysis may be biased, control data are important in providing adjustments derived from control-crossover analysis to case-crossover estimates, and are most important at higher levels of consumption prior to the event.


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Request Reprint E-Mail:     ccherpitel@arg.org

Phospholipase A2, Oxidative Stress, and Neurodegeneration in Binge Ethanol-Treated Organotypic Slice Cultures of Developing Rat Brain





Brain neurodamage from chronic binge ethanol (EtOH) exposure is linked to neuroinflammation and associated oxidative stress. Using rat organotypic hippocampal–entorhinal cortical (HEC) slice cultures of developing brain age, we reported that binge EtOH promotes release of a neuroinflammatory instigator, arachidonic acid (AA), concomitant with neurodegeneration, and that mepacrine, a global inhibitor of phospholipase A2 (PLA2) enzymes mobilizing AA from phospholipids, is neuroprotective. Here, we sought with binge EtOH-treated HEC cultures to establish that PLA2 activity is responsible in part for significant oxidative stress and to ascertain the PLA2 families responsible for AA release and neurodegeneration.
 
HEC slices, prepared from 1-week-old rats and cultured 2 to 2.5 weeks, were exposed to 100 mM EtOH over 6 successive days, with 4 daytime “withdrawals” (no EtOH). Brain 3-nitrotyrosinated (3-NT)- and 4-hydroxy-2-nonenal (4-HNE)-adducted proteins, oxidative stress footprints, were immunoassayed on days 3 through 6, and mepacrine's effect was determined on day 6. The effects of specific PLA2 inhibitors on neurodegeneration (propidium iodide staining) and AA release (ELISA levels in media) in the cultures were then determined. Also, the effect of JZL184, an inhibitor of monoacylglycerol lipase (MAGL) which is reported to mobilize AA from endocannabinoids during neuroinflammatory insults, was examined.
 
3-NT- and 4-HNE-adducted proteins were significantly increased by the binge EtOH exposure, consistent with oxidative stress, and mepacrine prevented the increases. The PLA2 inhibitor results implicated secretory PLA2 (group II sPLA2) and to some extent Ca2+-independent cytosolic PLA2 (group VI iPLA2) in binge EtOH-induced neurotoxicity and in AA release, but surprisingly, Ca2+-dependent cytosolic PLA2 (group IV cPLA2) did not appear important. Furthermore, unlike PLA2 inhibition, MAGL inhibition failed to prevent the neurodegeneration.

In these developing HEC slice cultures, pro-oxidative signaling via sPLA2 and iPLA2, but not necessarily cPLA2 or MAGL, is involved in EtOH neurotoxicity. This study provides further insights into neuroinflammatory phospholipase signaling and oxidative stress underlying binge EtOH-induced neurodegeneration in developing (adolescent age) brain in vitro.


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Request Reprint E-Mail:      mcollin@lumc.edu

Sunday, August 4, 2013

Alcohol Awareness Week 2013 runs 18-24 November; Alcohol Concern conferences




Alcohol Concern are promoting Alcohol Awareness Week (AAW) 2013 to take place from 18-24 November, encouraging local areas to promote conversations and awarenss of alcohol and its impact. 

Alcohol Concern have produced an outline of 
ideas and materials for organisations [pdf] who might wish to take part. Last year we reviewed Alcohol Awareness Week 2012 including a variety of twitter and local activity.  > > > >   Read More

Rare SERINC2 variants are specific for alcohol dependence in individuals of European descent.

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We have previously reported a top-ranked risk gene [i.e., serine incorporator 2 gene (SERINC2)] for alcohol dependence in individuals of European descent by analyzing the common variants in a genome-wide association study. In the present study, we comprehensively examined the rare variants [minor allele frequency ] in the NKAIN1-SERINC2 region to confirm our previous finding.


A discovery sample (1409 European-American patients with alcohol dependence and 1518 European-American controls) and a replication sample (6438 European-Australian family participants with 1645 alcohol-dependent probands) were subjected to an association analysis. A total of 39 903 individuals from 19 other cohorts with 11 different neuropsychiatric and neurological disorders served as contrast groups. The entire NKAIN1-SERINC2 region was imputed in all cohorts using the same reference panels of genotypes that included rare variants from the whole-genome sequencing data. We stringently cleaned the phenotype and genotype data, and obtained a total of about 220 single-nucleotide polymorphisms in individuals of European descent and about 450 single-nucleotide polymorphisms in the individuals of African descent.

Using a weighted regression analysis implemented in the program SCORE-Seq, we found a rare variant constellation across the entire NKAIN1-SERINC2 region that was associated with alcohol dependence in European-Americans and European-Australians), but not in African-Americans, and not associated with any other disorder examined. Association signals in this region came mainly from SERINC2, a gene that codes for an activity-regulated protein expressed in the brain that incorporates serine into lipids. In addition, 26 individual rare variants were nominally associated with alcohol dependence in European-Americans . The associations of five of these rare variants that lay within SERINC2 showed region-wide significance and 25 associations survived correction for a false discovery rate . The associations of two rare variants at SERINC2 were replicated in European-Australians .

We concluded that SERINC2 was a replicable and significant risk gene specific for alcohol dependence in individuals of European descent.

 


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Request Reprint E-Mail:      Lingjun.Zuo@yale.edu