PNAS alert!

Early first intoxication is a key risk factor for later binge drinking and alcohol addiction, for example, people with first alcohol intoxication before age 13 are more than 3 times more likely to develop alcohol addiction than college students aged 19 or later with alcoholism

On August 28, 2022, the team of Sidney B.

By screening more than 2,000 proteins in the hippocampus, the brain's control center, 72 proteins were found to have a two-fold increase in synaptic abundance after ethanol exposure, including mitochondrial proteins and proteins important for neuronal morphology

Early first-time alcoholism is a key risk factor for later alcoholism and the development of alcohol addiction
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The hippocampus is particularly vulnerable to alcohol intoxication during adolescence, and hippocampus-mediated behavior is sensitive to the acute effects of ethanol
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However, most studies have examined the effects of chronic ethanol exposure on the hippocampus and brain, and little is known about the acute neuronal correlates of key risk factors such as first-time intoxication
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The study uncovers alcohol-dependent molecular alterations that, in turn, can underlie persistent cellular changes following a single acute alcohol intoxication
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And qualitatively defined "persistent" as plastic, cellular changes that persisted beyond the original alcohol stimulus
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This persistent change is analogous to long-term potentiation (LTP), a type of plasticity that persists experimentally for hours but is thought to underlie learning and memory
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Persistent changes following acute alcohol exposure may underlie drug-related reward-related memory
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Therefore, identifying persistent changes in alcohol dependence is an important first step in understanding how acute alcohol consumption develops into chronic alcohol abuse
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Schematic diagram of the research process (figure from PNAS) The researchers then performed a synaptic proteome screen, since synapses are the main site of neuronal transmission, plasticity, and information storage
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So the researchers obtained isolated hippocampal slices from young mice (postnatal day P30, as prepubertal), found dozens of proteins, and further screened and identified cytoskeletal and mitochondrial proteins, including mitochondrial protein clusters and two structural proteins MAP6 and ankyrin-G, which significantly altered their synaptic abundance upon a single ethanol stimulation, indicating changes in neuronal morphology and mitochondrial trafficking following first exposure to alcohol
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Alcohol intake affects the plasticity of neuronal morphology (image from PNAS) Interestingly, the researchers used two-photon microscopy to image and characterize changes in morphology and mitochondrial dynamics, confirming 1) spine after acute alcohol administration Turnover was tripled and presynaptic boutons elimination increased, indicating increased structural plasticity; 2) mitochondrial mobility was significantly increased after acute ethanol intoxication
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This implicates mitochondrial transport and persistent effects of ethanol that may affect ethanol-related behavior, also validated in behavioral tests in Drosophila and mice, respectively
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In conclusion, to better understand brain changes in the transition from sporadic drinking to chronic alcohol abuse, the study identified differential effects of a single alcohol exposure on the molecular, cellular, and behavioral levels
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Similar to learning and memory processes, the idea is to discover long-lasting changes in memory that can mediate long-lasting alcohol rewards
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By imaging the brains of acutely alcohol-exposed mice, ethanol was found to cause lasting changes in synaptic morphology, initial axonal segments, and mitochondrial trafficking
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In Drosophila, specific knockout of mitochondrial trafficking abolished positive alcohol reward memory
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These mechanisms may reveal the reasons why early first alcohol intoxication is a key risk factor for later alcoholism and the development of alcohol addiction
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Original link: —END—The content is [iNature]