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Thread: Wake Forest Researchers Find Brain Region "Exquisitely" Sensitive to Alchol/Wake Forest Investigator Shows New Way That Alcohol Affects Brain/ Monkeys That Drink Heavily Develop Signs of Liver Disease, Wake Forest Study Shows

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    Senior Member Max's Avatar
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    Wake Forest Researchers Find Brain Region "Exquisitely" Sensitive to Alchol/Wake Forest Investigator Shows New Way That Alcohol Affects Brain/ Monkeys That Drink Heavily Develop Signs of Liver Disease, Wake Forest Study Shows

    Wake Forest Researchers Find Brain Region "Exquisitely" Sensitive to Alcohol
    Library: MED
    Keywords: ALCOHOL THALAMUS SLEEP DISRUPTS SPINDLE WAVES
    Description: Wake Forest University School of Medicine scientists are closing in on why drinking alcohol before bedtime paradoxically improves sleep that evening, but disrupts sleep during the early morning hours. (Research Society on Alcoholism)



    Embargoed for release until 4:15 p.m. PDT, (7:15 pm. EDT) Monday, July 1, 2002

    Wake Forest Researchers Find Brain Region "Exquisitely" Sensitive to Alcohol

    WINSTON-SALEM, N.C. -- Wake Forest University School of Medicine scientists are closing in on why drinking alcohol before bedtime paradoxically improves sleep that evening, but disrupts sleep during the early morning hours.

    In a presentation at the Research Society on Alcoholism in San Francisco, Dwayne W. Godwin, Ph.D. explained that a key brain region involved in sleep, the thalamus, is "exquisitely sensitive to alcohol."

    The cells in the thalamus possess an ion channel that behaves differently depending on the amount of alcohol that has been drunk. "Low doses of alcohol increase activity; high doses shut it down," said Godwin, associate professor of neurobiology and anatomy.

    Characteristic "spindle" brain waves are produced during what is called stage II sleep, which is transiently enhanced after alcohol consumption but is reduced later in the night . The spindle waves are generated in the thalamus and picked up in brain wave recordings.

    Godwin and colleagues Breck Carden, Ph.D., Jian Mu, M.D., and Nuwan Kurukulasuriya, Ph.D. in the Center for the Neurobehavioral Study of Alcohol are using the ferret as an animal model for sleep. The ferret thalamus produces the same characteristic spindle waves during stage II sleep as in people and reacts differently depending on the amount of alcohol.

    "Despite widespread interest in the influence of alcohol on sleep, the influence of alcohol on the thalamus had been uncharted territory," he said. Use of the ferret thalamus "is optimal for exploring such mechanisms, because they possess all of the necessary circuitry for the generation of spindle waves, which allows us to translate our studies to the situation in humans."

    Godwin said human studies have shown that just one drink before bed may decrease the time it takes to fall asleep. But in the second half of the night, sleep often is disrupted. "You may tend to wake up more and be a little more restless."

    When watched in the sleep laboratory, a drink before bed increases stage II sleep in the first part of the night and decreases that sleep in the second part of the night.

    In alcoholics, however, the decrease in stage II becomes more permanent. "Sleep disturbances are common in alcoholic patients, with a number of serious health consequences," Godwin said. "Chronic consumption can lead to a cycle where alcoholics increase their alcohol consumption in order to improve the subjectively more satisfying patterns of sleep," he said.

    The disrupted sleep pattern in alcoholics continues even into abstinence following treatment. "There is a significant relationship between alcoholics returning to consumption because of this sleep issue." In other words, one reason they go back to drinking may be an attempt to make their sleep feel more normal, or satisfying.

    In the animal model, the equivalent of a small bedtime dose of alcohol leads to enhancement of sleep early in the sleep period and disruption later in sleep. Godwin said that the ion channels underlie normal sleep spindles are functioning normally early in sleep, and but may be turned off later in sleep -- corresponding to those later periods of human sleep that are less restful.

    The ion channels are pores or passageways through the cell membranes of the neurons in the brain. Godwin and his colleagues are focusing on channels through which calcium ions flow from one side of the membrane to the other. The calcium ions carry an electrical charge and the charge "helps to determine whether or not the cell that possesses that channel will communicate with the next cell down the line in the chain of neurons."

    It is the calcium channels where the reaction differs depending on whether the thalamus is exposed to low doses or high doses of alcohol. "This channel is exquisitely sensitive to alcohol."

    The next step is to expose the ferret thalamus to continuing high doses of alcohol -- paralleling an alcoholic's consumption. "We are now exploring whether chronic consumption of alcohol may turn this channel off, not just acutely, but permanently," Godwin said.

    That permanent shutdown could explain why recovering alcoholics have trouble sleeping, and finding a means to alleviate it may help on the path to recovery.

    ###

    Contact: Robert Conn (rconn@wfubmc.edu), Jim Steele(jsteele@wfubmc.edu) or Mark Wright(mwright@wfubmc.edu) at (336) 716-4587
    For an electronic copy of this release by email, please call the contact number above.

    [This message was edited by Max on Jul 03, 2002 at 12:36 PM.]

    [This message was edited by Max on Jul 03, 2002 at 12:37 PM.]

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    Senior Member Max's Avatar
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    Wake Forest Investigator Shows New Way That Alcohol Affects Brain

    Wake Forest Investigator Shows New Way That Alcohol Affects Brain
    Library: MED
    Keywords: ALCOHOL BRAIN SYNAPSE BARBITURATES BENZODIAZEPINES
    Description: A Wake Forest University School of Medicine researcher today challenged a commonly accepted view on how alcohol acts in the brain in a plenary session presentation at a meeting in San Francisco. (Research Society on Alcoholism)



    Embargoed for Release at 10:15 a.m. PST Monday, July 1 (1:15 p.m. EDT)

    Wake Forest Investigator Shows New Way That Alcohol Affects Brain

    WINSTON-SALEM, N.C. -- A Wake Forest University School of Medicine researcher today challenged a commonly accepted view on how alcohol acts in the brain in a plenary session presentation at the Research Society on Alcoholism meeting in San Francisco.

    Jeffrey Weiner Ph. D., 2001 winner of the society's Young Investigator Award, said many scientists had thought for years that one of the ways that alcohol works was in much the same way as benzodiazepines (such as Valium and Xanax) or barbiturates (such as Nembutal). "But recent data from our laboratory and others challenge this concept and suggest that alcohol may have more complex effects."

    Weiner's work focuses on what is called the GABA synapse which he says contributes to many of alcohol's behavioral and cognitive effects, especially intoxication, dependence and withdrawal. "The GABA synapse is the main inhibitory synapse in the brain."

    The synapse is the gap between individual nerve cells in the brain. Nerve cells communicate with each other across these synapses by using chemical transmitters.

    GABA is one of several of those neurotransmitters, targeting what are known as GABA receptors. Barbiturates and benzodiazepines act only on these receptors, which is the source of their inhibitory or tranquilizing effect. Anesthetics also work on these receptors, as does alcohol.

    But Weiner, a member of Wake Forest's Center for the Neurobehavioral Study of Alcohol, recorded extensive evidence that alcohol also affects the nerve cell in the region before the synapse, which is called a pre-synaptic interaction.

    "Unless you really focus on all of these mechanisms, you don't get the full picture of what alcohol is doing," said Weiner, assistant professor of physiology and pharmacology. "By looking at both pre- and post- synaptic mechanisms, we discovered a whole new way that the sensitivity of the synapse to alcohol is regulated."

    That makes alcohol "very different" from the two comparison classes of drugs -- barbiturates and benzodiazepines.

    He said that this pre-synaptic activity may open the door for new drugs that might be used to treat alcoholism by focusing on that mechanism. For instance, he has already shown that a chemical called baclofen blocks the effect of alcohol on GABA synapses, but has no effect on benzodiazepines or barbiturates.

    "By doing this work, we gained new insight into what determines the overall sensitivity of the GABA synapse to alcohol," said Weiner. "That might help explain some of the individual variability and sensitivity to alcohol and aid in identifying individuals at risk of abusing alcohol."

    "Exploiting the targets we have found may aid in the development of pharmacotherapy," he said.

    In making the discovery, Weiner made use of a technology that was not widely used until the 1990s, known as the whole cell patch clamp electrophysiological method. The technology lets scientists focus on activity within individual brain cells.

    Using the technology in rat brains, Weiner was able to measure and document the variations in sensitivity to alcohol.

    The result of his research is a tentative conclusion that alcohol effects on GABA synapses "may involve a complex interplay between pre- and post-synaptic processes and likely differs fundamentally from the effects of other modulators" of these inhibitory synapses.

    Weiner is one of only six plenary speakers at the five-day meeting.

    ###

    Contact: Robert Conn (rconn@wfubmc.edu), Jim Steele (jsteele@wfubmc.edu) or Mark Wright (mwright@wfubmc.edu) at (336) 716-4587
    For an electronic copy of this release by email, please call the contact number above.

  3. #3
    Senior Member Max's Avatar
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    Monkeys That Drink Heavily Develop Signs of Liver Disease, Wake Forest Study Shows

    Monkeys That Drink Heavily Develop Signs of Liver Disease, Wake Forest Study Shows
    Library: MED
    Keywords: MONKEYS DRINKING ALCOHOL FATTY LIVER
    Description: Monkeys that choose to drink alcohol heavily develop early signs of alterations in the liver, according to research by a team of investigators from Wake Forest University School of Medicine.



    Embargoed For Release until 11:30 a.m. EDT (8:30 a.m. PDT) on Tuesday, July 2, 2000

    Monkeys That Drink Heavily Develop Signs of Liver Disease, Wake Forest Study Shows

    WINSTON-SALEM, N.C. -- Monkeys that choose to drink alcohol heavily develop early signs of alterations in the liver, according to research by a team of investigators from Wake Forest University School of Medicine.

    The research, presented today at the annual meeting of the Research Society on Alcoholism in San Francisco, describes a chemical found in the urine of monkeys also found in human alcoholics, and liver biopsies that show development of "fatty liver" -- another common finding in heavily drinking people.

    Carol C. Cunningham, Ph.D., professor of biochemistry said, "One of the unique features of using these monkeys as a model for alcoholic liver disease is that these monkeys self-administer alcohol."

    Some of the monkeys choose to only take a small amount of alcohol -- paralleling the social drinkers; some consume a moderate amount -- "like regular drinkers who are not in jeopardy of developing alcoholic liver disease," and some are heavy drinkers, who become intoxicated, most prone to changes in the liver.

    "In some respects, this group of monkeys mimic the human situation," he said, except "we don't have any monkeys that don't drink any (alcohol) -- they all drink something."

    First, Cunningham and his colleagues in the Center for the Neurobehavioral Study of Alcohol found evidence in the urine of "oxidative damage" to the liver. He explained that the metabolism of alcohol in the liver generates "reactive oxygen" which can damage liver tissue. To track that, they chose to follow damage to lipids, since cell structure is influenced by lipids.

    The damaged liver produces isoprostanes in the urine -- tiny pieces of oxidized lipids. "There is a dramatic increase in the level of these lipid products in heavy drinkers," Cunningham
    said. There are some isoprostanes in the urine of moderately drinking monkeys and only low amounts in the light drinkers.

    Second, biopsies of the livers of the heavily drinking monkeys found evidence of "fatty liver." He said, "That is very characteristic of what one sees in alcoholics."

    This is still a reversible stage of alcoholic liver disease.

    He said he has seen no evidence so far of cirrhosis of the liver. But in some more recent biopsies, Cunningham and his colleagues noted some evidence of increased collagen staining within the liver tissue, perhaps pointing to the development of collagen fibrosis. He said the researchers were continuing to take biopsies regularly to see if fibrosis or liver inflammation develop.

    Cunningham said that one of his goals in the study was to develop diagnostic procedures that are similar to those used in the clinic for humans. "Can we follow the progression of this disease in monkeys by looking at blood samples, urine samples and needle biopsies?"

    "The animal model may be very useful in understanding alcoholism," said Cunningham. "We've worked out some procedures that allow us to analyze during the periods they are on the ethanol (alcohol.) We can carry out these studies indefinitely."

    ###

    Contact: Robert Conn (rconn@wfubmc.edu), Jim Steele(jsteele@wfubmc.edu) or Mark Wright (mwright@wfubmc.edu) at (336) 716-4587.

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