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

Summary Alcohol intoxication at early ages is a risk factor for development of addictive behavior. To uncover neuronal molecular correlates of acute ethanol intoxication, we used stable-isotope labeled mice combined with quantitative mass spectrometry to screen over 2000 hippocampal proteins of whic...

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Published inbioRxiv
Main Authors Knabbe, Johannes, Protzmann, Jil, Schneider, Niklas, Dannehl, Dominik, Berger, Michael, Shoupeng Wei, Strahle, Christopher, Jaiswal, Astha, Lugani, Sophie, Zheng, Hongwei, Krüger, Marcus, Rohr, Karl, Spanagel, Rainer, Scholz, Henrike, Bilbao, Ainhoa, Engelhardt, Maren, Cambridge, Sidney B
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 09.09.2020
Subjects
Addictive behaviors
Alcohol
Ankyrins
Axons
Dopamine receptors
Ethanol
Hippocampus
Immunofluorescence
Intoxication
Mass spectroscopy
Mitochondria
Neuroimaging
Proteins
Proteomics
Reinforcement
Risk factors
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Summary:Summary Alcohol intoxication at early ages is a risk factor for development of addictive behavior. To uncover neuronal molecular correlates of acute ethanol intoxication, we used stable-isotope labeled mice combined with quantitative mass spectrometry to screen over 2000 hippocampal proteins of which 72 changed synaptic abundance up to two-fold after ethanol exposure. Among those were mitochondrial proteins and proteins important for neuronal morphology, including MAP6 and Ankyrin-G. Based on these candidate proteins, we found acute and lasting molecular, cellular, and behavioral changes following a single intoxication in alcohol-naïve mice. Immunofluorescence analysis revealed a 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 abolished conditioned alcohol preference in Drosophila. This introduces mitochondrial trafficking as a process implicated in reward learning, and highlights the potential of high-resolution proteomics to identify cellular mechanisms relevant for addictive behavior. Competing Interest Statement The authors have declared no competing interest. Footnotes * ↵+ shared first authors * https://heidata.uni-heidelberg.de/privateurl.xhtml?token=f88c8325-6f37-473d-856a-0af8109a2bba
DOI:10.1101/2020.09.09.289256