Chronic Voluntary Alcohol Consumption Alters Promoter Methylation and Expression of Fgf-2 and Fgfr1

Leonie Herburg, Mathias Rhein, Sabrina Kubinski, Ekaterini Kefalakes, Matar Levin Greenwald, Simona Gielman, Segev Barak, Helge Frieling, Claudia Grothe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Alcohol abuse accounts for 3.3 million deaths annually, rendering it a global health issue. Recently, fibroblast growth factor 2 (FGF-2) and its target, fibroblast growth factor receptor 1 (FGFR1), were discovered to positively regulate alcohol-drinking behaviors in mice. We tested whether alcohol intake and withdrawal alter DNA methylation of Fgf-2 and Fgfr1 and if there is a correlation regarding mRNA expression of these genes. Blood and brain tissues of mice receiving alcohol intermittently over a six-week period were analyzed using direct bisulfite sequencing and qRT-PCR analysis. Assessment of Fgf-2 and Fgfr1 promoter methylation revealed changes in the methylation of cytosines in the alcohol group compared with the control group. Moreover, we showed that the altered cytosines coincided with binding motives of several transcription factors. We also found that Fgf-2 and Fgfr1 gene expression was significantly decreased in alcohol-receiving mice compared with control littermates, and that this effect was specifically detected in the dorsomedial striatum, a brain region involved in the circuitry of the reward system. Overall, our data showed alcohol-induced alterations in both mRNA expression and methylation pattern of Fgf-2 and Fgfr1. Furthermore, these alterations showed a reward system regional specificity, therefore, resembling potential targets for future pharmacological interventions.

Original languageEnglish
Article number3336
JournalInternational Journal of Molecular Sciences
Issue number4
StatePublished - Feb 2023


FundersFunder number
Deutsche Forschungsgemeinschaft857/29-1
Israel Science Foundation508/20


    • FGF-2
    • FGFR1
    • addiction
    • alcohol
    • epigenetic alteration
    • mesolimbic system


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