Global brain c-Fos profiling reveals major functional brain networks rearrangements after alcohol reexposure

Many fundamental questions on alcohol use disorder (AUD) are frequently difficult to address by examining a single brain structure, but should be viewed from the whole brain perspective. c-Fos is a marker of neuronal activation. Global brain c-Fos profiling in rodents represents a promising platform...

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Main Authors: Marzena Stefaniuk, Monika Pawłowska, Marcin Barański, Klaudia Nowicka, Zbigniew Zieliński, Łukasz Bijoch, Diana Legutko, Piotr Majka, Sylwia Bednarek, Natalia Jermakow, Daniel Wójcik, Leszek Kaczmarek
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996123000207
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author Marzena Stefaniuk
Monika Pawłowska
Marcin Barański
Klaudia Nowicka
Zbigniew Zieliński
Łukasz Bijoch
Diana Legutko
Piotr Majka
Sylwia Bednarek
Natalia Jermakow
Daniel Wójcik
Leszek Kaczmarek
author_facet Marzena Stefaniuk
Monika Pawłowska
Marcin Barański
Klaudia Nowicka
Zbigniew Zieliński
Łukasz Bijoch
Diana Legutko
Piotr Majka
Sylwia Bednarek
Natalia Jermakow
Daniel Wójcik
Leszek Kaczmarek
author_sort Marzena Stefaniuk
collection DOAJ
description Many fundamental questions on alcohol use disorder (AUD) are frequently difficult to address by examining a single brain structure, but should be viewed from the whole brain perspective. c-Fos is a marker of neuronal activation. Global brain c-Fos profiling in rodents represents a promising platform to study brain functional networks rearrangements in AUD.We used a mouse model of alcohol drinking in IntelliCage. We trained mice to voluntarily drink alcohol, next subjected them to withdrawal and alcohol reexposure. We have developed a dedicated image computational workflow to identify c-Fos-positive cells in three-dimensional images obtained after whole-brain optical clearing and imaging in the light-sheet microscope.We provide a complete list of 169 brain structures with annotated c-Fos expression. We analyzed functional networks, brain modularity and engram index. Brain c-Fos levels in animals reexposed to alcohol were different from both control and binge drinking animals. Structures involved in reward processing, decision making and characteristic for addictive behaviors, such as precommissural nucleus, nucleus Raphe, parts of colliculus and tecta stood out particularly. Alcohol reexposure leads to a massive change of brain modularity including a formation of numerous smaller functional modules grouping structures involved in addiction development.Binge drinking can lead to substantial functional remodeling in the brain. We provide a list of structures that can be used as a target in pharmacotherapy but also point to the networks and modules that can hold therapeutic potential demonstrated by a clinical trial in patients.
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spelling doaj.art-974c643861564b6485e502d0bae1a77a2023-02-13T04:06:52ZengElsevierNeurobiology of Disease1095-953X2023-03-01178106006Global brain c-Fos profiling reveals major functional brain networks rearrangements after alcohol reexposureMarzena Stefaniuk0Monika Pawłowska1Marcin Barański2Klaudia Nowicka3Zbigniew Zieliński4Łukasz Bijoch5Diana Legutko6Piotr Majka7Sylwia Bednarek8Natalia Jermakow9Daniel Wójcik10Leszek Kaczmarek11Laboratory of Neurobiology, Nencki Institute, BRAINCITY, Warsaw, Poland; Corresponding author at: Nencki Institute, BRAINCITY, Warsaw 02-093, Poland.Laboratory of Neurobiology, Nencki Institute, BRAINCITY, Warsaw, Poland; Institute of Experimental Physics, Section of Optics, Warsaw University, Warsaw, PolandLaboratory of Neurobiology, Nencki Institute, BRAINCITY, Warsaw, PolandLaboratory of Neurobiology, Nencki Institute, BRAINCITY, Warsaw, PolandLaboratory of Neurobiology, Nencki Institute, BRAINCITY, Warsaw, PolandLaboratory of Neurobiology, Nencki Institute, BRAINCITY, Warsaw, Poland; Laboratory of Neuronal Plasticity, Nencki Institute, BRAINCITY, Warsaw, PolandLaboratory of Neurobiology, Nencki Institute, BRAINCITY, Warsaw, PolandLaboratory of Neuroinformatics, Nencki Institute, Warsaw, PolandLaboratory of Neuroinformatics, Nencki Institute, Warsaw, PolandLaboratory of Neuroinformatics, Nencki Institute, Warsaw, PolandLaboratory of Neuroinformatics, Nencki Institute, Warsaw, PolandLaboratory of Neurobiology, Nencki Institute, BRAINCITY, Warsaw, PolandMany fundamental questions on alcohol use disorder (AUD) are frequently difficult to address by examining a single brain structure, but should be viewed from the whole brain perspective. c-Fos is a marker of neuronal activation. Global brain c-Fos profiling in rodents represents a promising platform to study brain functional networks rearrangements in AUD.We used a mouse model of alcohol drinking in IntelliCage. We trained mice to voluntarily drink alcohol, next subjected them to withdrawal and alcohol reexposure. We have developed a dedicated image computational workflow to identify c-Fos-positive cells in three-dimensional images obtained after whole-brain optical clearing and imaging in the light-sheet microscope.We provide a complete list of 169 brain structures with annotated c-Fos expression. We analyzed functional networks, brain modularity and engram index. Brain c-Fos levels in animals reexposed to alcohol were different from both control and binge drinking animals. Structures involved in reward processing, decision making and characteristic for addictive behaviors, such as precommissural nucleus, nucleus Raphe, parts of colliculus and tecta stood out particularly. Alcohol reexposure leads to a massive change of brain modularity including a formation of numerous smaller functional modules grouping structures involved in addiction development.Binge drinking can lead to substantial functional remodeling in the brain. We provide a list of structures that can be used as a target in pharmacotherapy but also point to the networks and modules that can hold therapeutic potential demonstrated by a clinical trial in patients.http://www.sciencedirect.com/science/article/pii/S0969996123000207AlcoholBinge drinkingLight-sheet microscopyC-FosIntelliCage
spellingShingle Marzena Stefaniuk
Monika Pawłowska
Marcin Barański
Klaudia Nowicka
Zbigniew Zieliński
Łukasz Bijoch
Diana Legutko
Piotr Majka
Sylwia Bednarek
Natalia Jermakow
Daniel Wójcik
Leszek Kaczmarek
Global brain c-Fos profiling reveals major functional brain networks rearrangements after alcohol reexposure
Neurobiology of Disease
Alcohol
Binge drinking
Light-sheet microscopy
C-Fos
IntelliCage
title Global brain c-Fos profiling reveals major functional brain networks rearrangements after alcohol reexposure
title_full Global brain c-Fos profiling reveals major functional brain networks rearrangements after alcohol reexposure
title_fullStr Global brain c-Fos profiling reveals major functional brain networks rearrangements after alcohol reexposure
title_full_unstemmed Global brain c-Fos profiling reveals major functional brain networks rearrangements after alcohol reexposure
title_short Global brain c-Fos profiling reveals major functional brain networks rearrangements after alcohol reexposure
title_sort global brain c fos profiling reveals major functional brain networks rearrangements after alcohol reexposure
topic Alcohol
Binge drinking
Light-sheet microscopy
C-Fos
IntelliCage
url http://www.sciencedirect.com/science/article/pii/S0969996123000207
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