A research team from the University of Cologne and the Universities of Mannheim and Heidelberg has found that even a single administration of alcohol permanently alters the morphology of neurons. In particular, the structure of synapses, as well as the dynamics of mitochondria, the powerhouses of the cell, are influenced by alcohol. Using the genetic model system of the fruit fly Drosophila melanogaster, Professor Henrike Scholz and his team members Michèle Tegtmeier and Michael Berger showed that changes in the migration of mitochondria to synapses reduce the rewarding effect of l ‘alcohol. These results suggest that even a single drinking event can lay the foundation for alcohol addiction. The study ‘Single-dose ethanol intoxication causes acute and long-lasting neuronal changes in the brain’ has appeared in PNAS (Proceedings of the National Academy of Sciences).
What changes in the brain accompany the transition from sporadic to chronic alcohol abuse? This is the question explored by a joint research project with working groups from the University of Mannheim-Heidelberg and the University of Cologne. Most scientific research has examined the effects of chronic alcohol consumption on the hippocampus, the control center of our brain. Because of this, little is known about the acute neural interactions of critical risk factors, such as a first alcohol intoxication at an early age, explained Henrike Scholz: “We set out to discover ethanol-dependent molecular changes. These, in in turn, provide the basis for permanent cellular changes following a single acute ethanol intoxication. The effects of a single alcohol administration were examined at the molecular, cellular, and behavioral levels.” The working hypothesis was that, similar to memory formation after a single lesson, a single administration of ethanol would form a positive association with alcohol.
The team tested their hypothesis using research in fruit fly and mouse models and found ethanol-induced changes in two areas: mitochondrial dynamics and the balance between neuron synapses. Mitochondria provide energy to cells and especially to nerves. In order to optimally deliver energy to cells, mitochondria move. Mitochondrial movement was altered in ethanol-treated cells. The chemical balance between certain synapses was also altered. These changes were permanent and confirmed by behavioral changes in animals: mice and fruit flies showed increased alcohol consumption and relapse to alcohol later in life.
Morphological remodeling of neurons is a known basis for learning and memory. These so-called cellular plasticity mechanisms, which are central to learning and memory, are also thought to be at the core of forming associative memories for drug-related rewards. Therefore, some of the observed morphological changes may influence ethanol-related memory formation. Along with the migration of mitochondria to neurons, which are also important for synaptic transmission and plasticity, the researchers speculate that these ethanol-dependent cellular changes are critical for the development of addictive behaviors.
“It is remarkable that the cellular processes that contribute to such complex reward behavior are conserved across species, suggesting a similar role in humans,” said Henrike Scholz. “It could be a possible general cellular process essential for learning and memory.”
Both of these observed mechanisms could explain observations in mice that a single intoxication experience can increase alcohol consumption and alcohol relapse later in life. “These mechanisms may even be relevant to the observation in humans that first alcohol intoxication at an early age is a critical risk factor for later alcohol intoxication and the development of alcohol addiction” , Professor Scholz explained. “This means that identifying long-lasting ethanol-dependent changes is an important first step in understanding how acute drinking can turn into chronic alcohol abuse.”
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