Universität zu Köln

Knabbe, Johannes ORCID: 0000-0003-3170-111X, Protzmann, Jil ORCID: 0000-0002-6884-5646, Schneider, Niklas, Berger, Michael, Dannehl, Dominik, Wei, Shoupeng, Strahle, Christopher, Tegtmeier, Michele, Jaiswal, Astha, Zheng, Hongwei, Krueger, Marcus, Rohr, Karl, Spanagel, Rainer, Bilbao, Ainhoa, Engelhardt, Maren ORCID: 0000-0001-8020-6604, Scholz, Henrike and Cambridge, Sidney B. (2022). Single-dose ethanol intoxication causes acute and lasting neuronal changes in the brain. Proc. Natl. Acad. Sci. U. S. A., 119 (25). WASHINGTON: NATL ACAD SCIENCES. ISSN 1091-6490

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Abstract

Alcohol intoxication at early ages 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 combined with quantitative mass spectrometry to screen more than 2,000 hippocampal proteins, of which 72 changed synaptic abundance up to twofold 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-naive 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 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 for addictive behavior.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Knabbe, Johannes UNSPECIFIED orcid.org/0000-0003-3170-111X UNSPECIFIED Protzmann, Jil UNSPECIFIED orcid.org/0000-0002-6884-5646 UNSPECIFIED Schneider, Niklas UNSPECIFIED UNSPECIFIED UNSPECIFIED Berger, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Dannehl, Dominik UNSPECIFIED UNSPECIFIED UNSPECIFIED Wei, Shoupeng UNSPECIFIED UNSPECIFIED UNSPECIFIED Strahle, Christopher UNSPECIFIED UNSPECIFIED UNSPECIFIED Tegtmeier, Michele UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaiswal, Astha UNSPECIFIED UNSPECIFIED UNSPECIFIED Zheng, Hongwei UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Rohr, Karl UNSPECIFIED UNSPECIFIED UNSPECIFIED Spanagel, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Bilbao, Ainhoa UNSPECIFIED UNSPECIFIED UNSPECIFIED Engelhardt, Maren UNSPECIFIED orcid.org/0000-0001-8020-6604 UNSPECIFIED Scholz, Henrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Cambridge, Sidney B. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-689971
DOI:	10.1073/pnas.2122477119
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	119
Number:	25
Date:	2022
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	1091-6490
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language AXON INITIAL SEGMENT; ALCOHOL-USE; RISK-FACTOR; IN-VIVO; AGE; MITOCHONDRIA; PLASTICITY; MOUSE; HIPPOCAMPUS; TRANSPORT Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68997