A dual-omics approach on the effects of fibroblast growth factor-2 (FGF-2) on ventral tegmental area dopaminergic neurons in response to alcohol consumption in mice

Leonie Hose, Alina Katharina Langenhagen, Ekaterini Kefalakes, Theresa Schweitzer, Sabrina Kubinski, Segev Barak, Andreas Pich, Claudia Grothe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Harmful alcohol consumption is a major socioeconomic burden to the health system, as it can be the cause of mortality of heavy alcohol drinkers. The dopaminergic (DAergic) system is thought to play an important role in the pathogenesis of alcohol drinking behaviour; however, its exact role remains elusive. Fibroblast growth factor 2 (FGF-2), a neurotrophic factor, associated with both the DAergic system and alcohol consumption, may play an important role in DAergic neuroadaptations during alcohol abuse. Within this study, we aimed to clarify the role of endogenous FGF-2 on the DAergic system and whether there is a possible link to alcohol consumption. We found that lack of FGF-2 reduces the alcohol intake of mice. Transcriptome analysis of DAergic neurons revealed that FGF-2 knockout (FGF-2 KO) shifts the molecular fingerprint of midbrain dopaminergic (mDA) neurons to DA subtypes of the ventral tegmental area (VTA). In line with this, proteomic changes predominantly appear also in the VTA. Interestingly, these changes led to an altered regulation of the FGF-2 signalling cascades and DAergic pathways in a region-specific manner, which was only marginally affected by voluntary alcohol consumption. Thus, lack of FGF-2 not only affects the gene expression but also the proteome of specific brain regions of mDA neurons. Our study provides new insights into the neuroadaptations of the DAergic system during alcohol abuse and, therefore, comprises novel targets for future pharmacological interventions.

Original languageEnglish
Pages (from-to)1519-1535
Number of pages17
JournalEuropean Journal of Neuroscience
Volume59
Issue number7
DOIs
StatePublished - Apr 2024

Funding

FundersFunder number
Deutsche ForschungsgemeinschaftGR 857/29‐1
Deutsche Forschungsgemeinschaft
Israel Science FoundationGR 508/20
Israel Science Foundation

    Keywords

    • FGF
    • alcohol addiction
    • alcoholism
    • brain reward system
    • dopamine receptors

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