A single dose of alcohol can change your brain

Overview: A single dose of alcohol permanently alters synaptic structure and mitochondrial dynamics, researchers report.

sauce: University of Cologne

A team of researchers from the Universities of Cologne, Mannheim and Heidelberg found that even a single dose of alcohol permanently altered the morphology of neurons.

In particular, synaptic structure and mitochondrial dynamics are affected by alcohol. Drosophila melanogaster Using the Drosophila genetic model system, Professor Henrike Scholz and her team Her members Michèle Tegtmeier and Michael Berger showed that alterations in mitochondrial movement at synapses reduce the rewarding effects of alcohol .

These results suggest that even a single consumption event can lay the groundwork for alcohol addiction.

This research PNAS .

What brain changes accompany the transition from sporadic drinking to chronic alcohol abuse?

That is the question investigated by a joint research project with working groups from the Universities of Mannheim Heidelberg and the Universities of Cologne. Most scientific studies have examined the effects of chronic alcohol consumption on the brain’s control center, the hippocampus. Henrike Scholz explained that little is known about

“We set out to discover ethanol-dependent molecular changes. These, in turn, provide the basis for permanent cellular changes following a single acute ethanol intoxication.” Effects were examined at the molecular, cellular and behavioral level,” Scholz said.

The working hypothesis was that a single dose of ethanol formed a positive association with alcohol, similar to memory formation after a single lesson.

The team tested that hypothesis using studies in Drosophila and mouse models and found ethanol-induced changes in two areas: mitochondrial dynamics and the balance between neuronal synapses. Mitochondria provide energy to cells, especially nerve cells. Mitochondria work to optimally deliver energy to cells.

Mitochondrial movement was disturbed in ethanol-treated cells. The chemical balance between specific synapses was also disturbed. These changes remained permanent and were confirmed by changes in animal behavior.

Morphological remodeling of neurons is a well-known basis of learning and memory. These so-called cellular plasticity mechanisms are central to learning and memory, and are also believed to be central to the formation of associative memory for drug-related rewards. Therefore, some of the observed morphological changes may affect ethanol-related memory formation.

Along with mitochondrial movement within neurons, which is also important for synaptic transmission and plasticity, researchers speculate that these ethanol-dependent cellular changes are important for the development of addictive behaviors.

“It is remarkable that the cellular processes contributing to such complex reward behaviors are conserved across species, suggesting a similar role in humans,” said Scholz. “This could be a common cellular process essential for learning and memory.”

Both of the observed mechanisms can explain observations in mice that one addiction experience can increase alcohol consumption and subsequent relapses of alcohol.

“These mechanisms may even be relevant to human observations that initial alcoholism at an early age is a significant risk factor for the development of subsequent alcoholism and alcoholism,” says Professor Scholz. explained.

“This means that identifying changes in sustained ethanol dependence is an important first step in understanding how acute drinking turns into chronic alcohol abuse. ”

See also

About this neuroscience research news

author: press office
sauce: University of Cologne
contact: Press Office – University of Cologne
image: image is public domain

Original research: closed access.
“Single-dose ethanol intoxication causes acute and persistent neuronal changes in the brain” Johannes Knabbe et al. PNAS

Overview

Single-dose ethanol intoxication causes acute and persistent neuronal changes in the brain

Alcoholism 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 mice in combination with quantitative mass spectrometry to screen over 2,000 hippocampal proteins. 72 of them had up to a 2-fold change in synaptic abundance after ethanol exposure. These included mitochondrial proteins and proteins important for neuronal morphology, such as MAP6 and ankyrin G.

Based on these candidate proteins, we discovered acute and persistent molecular, cellular, and behavioral changes following a single intoxication in alcohol-naive mice. Immunofluorescence analysis revealed shortening of the first segment of axons. His two-photon in vivo imaging in longitudinal direction showed increased synaptic dynamics and mitochondrial trafficking in axons.Knockdown of mitochondrial trafficking in dopaminergic neurons abolished conditioned alcohol preference Drosophila Flies.

This study introduces mitochondrial trafficking as a process involved in reward learning and highlights the potential of high-resolution proteomics to identify cellular mechanisms associated with addictive behavior.