summary: A single dose of alcohol permanently alters the structure of synapses and the dynamics of mitochondria, the researchers report.
Source: University of Cologne
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.
Notably, the structure of synapses as well as the dynamics of mitochondria are affected by alcohol. Using a genetic model system of the fruit fly Drosophila melanogaster, Professor Dr. Heinrich Scholz and his team members Michel Tegtmeier and Michael Berger showed that changes in mitochondria migration at the synapse reduce the rewarding effects of alcohol.
These results suggest that a single consumption event can lay the foundation for alcohol addiction.
revealed in the study PNAS ,
What changes in the brain occur with the transition from sporadic drinking to chronic alcohol abuse?
That is the question explored by a joint research project with working groups at 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 neuronal interactions of important risk factors, such as first-time alcohol intoxication at an early age, explained Heinrich Scholz.
“We set out to discover ethanol-dependent molecular changes. These, in turn, provide the basis for permanent cellular changes following single acute ethanol intoxication. The effects of single alcohol administration were examined at the molecular, cellular and behavioral levels. ,” said Scholz.
The working hypothesis was that, similar to the formation of a memory after a lesson, a single administration of ethanol would create a positive association with alcohol.
The team tested their hypothesis using research in 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. To better distribute energy to cells, mitochondria move.
The movement of mitochondria is inhibited in cells treated with ethanol. The chemical balance between some synapses was also disturbed. These changes remained permanent and were confirmed by changes in behavior in the animals: rats and fruit flies showed increased alcohol consumption and alcohol intake later in life.
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 at the origin of the formation of associative memories for drug-related rewards. Therefore, some of the observed morphological changes may affect ethanol-related memory formation.
Along with the migration of mitochondria into neurons, which are also important for synaptic transmission and plasticity, the researchers speculate that these ethanol-dependent cellular changes are important 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,” Scholz said. “This may be a potentially common cellular process required for learning and memory.”
Both mechanisms observed may explain observations made in rats that a single intoxication experience can increase alcohol consumption and lead to alcohol relapse later in life.
“These mechanisms may also be relevant to the observation in humans that the first alcohol intoxication at a young age is an important risk factor for the development of later alcohol intoxication and alcohol addiction,” explained Professor Scholz.
“This means that identifying permanent ethanol-dependent changes is an important first step in understanding how acute drinking can lead to chronic alcohol abuse.”
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About this neuroscience research news
Author: Press Office
Source: University of Cologne
contact: Press Office – University of Cologne
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Basic Research: closed access.
“Single-dose ethanol intoxication causes acute and permanent neuronal changes in the brain” by Johannes Nineby et al. PNAS
essence
Single-dose ethanol intoxication causes acute and permanent neuronal changes in the brain
Alcohol intoxication at an early age is a risk factor for the development of addictive behavior.
To uncover neuronal molecular correlates of acute ethanol intoxication, we used stable-isotope-labeled rats combined with quantitative mass spectrometry to screen more than 2,000 hippocampal proteins, 72 of which underwent ethanol exposure. Changed synaptic abundance by up to twofold. Among them were mitochondrial proteins and proteins important for neuronal morphology, including MAP6 and ankyrin-G.
On the basis of these candidate proteins, we found acute and permanent molecular, cellular and behavioral changes after single intoxication in alcohol-naive rats. Immunofluorescence analysis revealed shortening of axon initial segments. Longitudinal two-photon in vivo imaging showed increased synaptic dynamics and mitochondrial trafficking in axons. Knockdown of mitochondrial trafficking in dopaminergic neurons abolishes conditioned alcohol preference Drosophila flies.
This study introduces mitochondrial trafficking as a process implicated in reward learning and highlights the potential of high-resolution proteomics to identify cellular mechanisms relevant to addictive behavior.
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