A single administration of alcohol can permanently alter the morphology of neurons

A single administration of alcohol can permanently alter the morphology of neurons

A team of researchers from the University of Cologne and the universities of Mannheim and Heidelberg have discovered that even a single administration of alcohol permanently changes the morphology of neurons. In particular, the structure of the synapses and the dynamics of the mitochondria - the power plants of the cell - are influenced by alcohol. Using the genetic model system of the fruit fly Drosophila melanogaster, Prof. Dr. Henrike Scholz and her teammates Michèle Tegtmeier and Michael Berger found that changes in the migration of mitochondria in the synapses reduce the rewarding effects of alcohol. These results suggest that even a single consumption event can lay the foundation for alcohol dependence. The study “Single-dose ethanol intoxication causes acute and persistent neuronal changes in the brain” has been published in PNAS (Proceedings of the National Academy of Sciences).

What changes in the brain accompany the transition from sporadic drinking to chronic alcohol abuse? A joint research project with working groups from the University of Mannheim-Heidelberg and the University of Cologne investigated this question. Most scientific research has examined the effects of chronic alcohol consumption on the hippocampus - the control center of our brain. Therefore, little is known about the acute neuronal interactions of critical risk factors, such as a first alcohol poisoning at a young age, explains Henrike Scholz: "We set out to look for ethanol-dependent molecular changes. These in turn form the basis for lasting cellular changes after a single acute ethanol poisoning. The effects of a single alcohol administration were investigated 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 by studying fruit flies and mouse models and found ethanol-induced changes in two areas: mitochondrial dynamics and the balance between synapses in neurons. Mitochondria supply cells and especially nerve cells with energy. In order to optimally deliver energy to the cells, the mitochondria move. In the cells treated with ethanol, the movement of the mitochondria was disrupted. The chemical balance between certain synapses was also disrupted. These changes remained permanent and were confirmed by behavioral changes in the animals: mice and fruit flies showed increased alcohol consumption and alcohol relapses later in life.

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Morphological remodeling of neurons is a well-known basis for learning and memory. These so-called cellular plasticity mechanisms, which are central to learning and memory, are also thought to be central to the formation of associative memories for drug-related rewards. Therefore, some of the observed morphological changes may influence ethanol-related memory formation. Together with the migration of mitochondria into neurons, which are also important for synaptic transmission and plasticity, the researchers suspect that these ethanol-dependent cellular changes are crucial for the development of addictive behavior.

It is noteworthy that the cellular processes that contribute to such complex reward behavior are conserved across species, suggesting a similar role in humans. It could be a possible general cellular process that is essential for learning and memory.”

Prof. Dr. Henrike Scholz

Both observed mechanisms could explain observations made in mice that a single intoxication experience can increase alcohol consumption and alcohol relapse later in life. “These mechanisms could even be relevant to the observation in humans that the first alcohol intoxication at an early age is a critical risk factor for later alcohol intoxication and the development of alcohol dependence,” explains Professor Scholz. "This means that identifying persistent ethanol-dependent changes is an important first step in understanding how acute drinking can lead to chronic alcohol abuse."

Source:

University of Cologne

Reference:

Knabbe, J., et al. (2022) Single-dose ethanol poisoning causes acute and permanent neuronal changes in the brain. PNAS. doi.org/10.1073/pnas.2122477119.

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