Alcohol-Related Neurodegeneration and Recovery: Mechanisms From Animal Models

Summary

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Human studies have found alcoholics to have a smaller brain size than moderate drinkers; however, these studies are complicated by many uncontrollable factors, including timing and amount of alcohol use. Animal experiments, which can control many factors, have established that alcohol can cause damage to brain cells (i.e., neurons), which results in their loss of structure or function (i.e., neurodegeneration) in multiple brain regions, similar to the damage found in human alcoholics. In addition, animal studies indicate that inhibition of the creation of neurons (i.e., neurogenesis) and other brain-cell genesis contributes to alcoholic neurodegeneration. Animal studies also suggest that neurodegeneration changes cognition, contributing to alcohol use disorders. Risk factors such as adolescent age and genetic predisposition toward alcohol consumption worsen neurodegeneration. Mild impairment of executive functions similar to that found in humans occurs in animals following binge alcohol treatment. Thus, animal studies suggest that heavy alcohol use contributes to neurodegeneration and the progressive loss of control over drinking. Despite the negative consequences of heavy drinking, there is hope of recovery with abstinence, which in animal models can result in neural stem-cell proliferation and the formation of new neurons and other brain cells, indicative of brain growth.

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Alcohol-Related Neurodegeneration and Recovery: Mechanisms From Animal Models

The discovery that alcoholic humans have small brains is confounded by not knowing what the brain size was before alcoholism. Smaller human alcoholic brains could be attributed to smaller brain volume increasing risk for becoming alcoholic, alcoholinduced brain shrinkage, or both. Because mammalian brains are similar, animal studies allow investigation of the brain before, during, and after alcohol intoxication, as well as investigation of other factors that complicate understanding human disease. Animal studies continue to be used to model human responses in order to understand how to better prevent and reverse human problems. One key finding from animal studies is that high blood alcohol levels which occur with binge drinking and alcoholism can cause neurodegeneration without any nutritional or other deficiency (Crews and Nixon 2008).

Neurodegeneration is defined as the loss of structure or function of brain cells, including death of neurons and other cellular components. Alcoholic neurodegeneration is subtle, widespread, and varied but can be compared with other neurodegenerative diseases (Rosenbloom and Pfefferbaum 2008). This article will review studies on animal models of alcoholism that indicate multiple mechanisms of alcohol neurodegeneration and loss of key brain functions related to addiction. Other animal studies of brain regeneration in abstinent alcoholtreated animals will be related to human studies investigating changes in the abstinent alcoholic human brain. The integration of animal experimentation with human clinical discoveries supports the significant role of alcohol abuse and abstinence following chronic alcohol abuse in changing brain structure that corresponds with changes in cognition.

ADVANTAGES OF USING ANIMAL MODELS TO STUDY ALCOHOLIC NEUROD...

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