Dysregulated Methylation Patterns in Exon IV of the Brain-Derived Neurotrophic Factor (BDNF) Gene in Nicotine Dependence and Changes in BDNF Plasma Levels During Smoking Cessation
IntroductionSeveral studies reported dysregulated protein levels of brain-derived neurotrophic factor (BDNF) in smokers and during cessation. However, the epigenetic regulation of the BDNF gene has not yet been investigated. We measured the plasma levels of BDNF and the epigenetic regulation of exon...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2022.897801/full |
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| author | Kerim Abdelkhalek Mathias Rhein Maximilian Deest Vanessa Buchholz Stefan Bleich Ralf Lichtinghagen Benjamin Vyssoki Helge Frieling Marc Muschler Phileas Johannes Proskynitopoulos Alexander Glahn |
| author_facet | Kerim Abdelkhalek Mathias Rhein Maximilian Deest Vanessa Buchholz Stefan Bleich Ralf Lichtinghagen Benjamin Vyssoki Helge Frieling Marc Muschler Phileas Johannes Proskynitopoulos Alexander Glahn |
| author_sort | Kerim Abdelkhalek |
| collection | DOAJ |
| description | IntroductionSeveral studies reported dysregulated protein levels of brain-derived neurotrophic factor (BDNF) in smokers and during cessation. However, the epigenetic regulation of the BDNF gene has not yet been investigated. We measured the plasma levels of BDNF and the epigenetic regulation of exon IV of the BDNF gene in smokers compared to healthy controls over a cessation period of 14 days.MethodWe measured BDNF plasma levels and BDNF promoter methylation in 49 smokers and 51 non-smokers at baseline, day 7, and day 14 of smoking cessation. Mean methylation levels of 11 Cytosine Guanosine dinucleotides of exon IV of the BDNF gene were determined via bisulfite sequencing.ResultsBDNF plasma and methylation levels were significantly lower in healthy controls when compared with smokers across all time points. BDNF levels for smokers decreased significantly during the cessation period. Comparing the sexes, female smokers showed significantly lower plasma BDNF levels than healthy controls at baseline and over 14 days of cessation. Male and female smokers showed significantly higher mean methylation rates than non-smokers at baseline. In male smokers, mean methylation levels decreased significantly during the cessation period.ConclusionOur findings replicate the findings of previous studies that BDNF plasma levels are altered in smokers. Furthermore, BDNF expression and gene methylation are altered during the first 14 days of cessation. Our novel findings of dysregulated methylation patterns in exon IV of the BDNF gene further support the thesis that BDNF plays a role in nicotine dependence. |
| first_indexed | 2024-12-12T14:21:34Z |
| format | Article |
| id | doaj.art-f9789a4e711c4f1c803fee4431ece24b |
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| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-12T14:21:34Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-f9789a4e711c4f1c803fee4431ece24b2022-12-22T00:21:48ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402022-06-011310.3389/fpsyt.2022.897801897801Dysregulated Methylation Patterns in Exon IV of the Brain-Derived Neurotrophic Factor (BDNF) Gene in Nicotine Dependence and Changes in BDNF Plasma Levels During Smoking CessationKerim Abdelkhalek0Mathias Rhein1Maximilian Deest2Vanessa Buchholz3Stefan Bleich4Ralf Lichtinghagen5Benjamin Vyssoki6Helge Frieling7Marc Muschler8Phileas Johannes Proskynitopoulos9Alexander Glahn10Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyDepartment of Clinical Chemistry, Hannover Medical School, Hannover, GermanyBoard of Trustees for Psychosocial Services in Vienna, Vienna, AustriaDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyIntroductionSeveral studies reported dysregulated protein levels of brain-derived neurotrophic factor (BDNF) in smokers and during cessation. However, the epigenetic regulation of the BDNF gene has not yet been investigated. We measured the plasma levels of BDNF and the epigenetic regulation of exon IV of the BDNF gene in smokers compared to healthy controls over a cessation period of 14 days.MethodWe measured BDNF plasma levels and BDNF promoter methylation in 49 smokers and 51 non-smokers at baseline, day 7, and day 14 of smoking cessation. Mean methylation levels of 11 Cytosine Guanosine dinucleotides of exon IV of the BDNF gene were determined via bisulfite sequencing.ResultsBDNF plasma and methylation levels were significantly lower in healthy controls when compared with smokers across all time points. BDNF levels for smokers decreased significantly during the cessation period. Comparing the sexes, female smokers showed significantly lower plasma BDNF levels than healthy controls at baseline and over 14 days of cessation. Male and female smokers showed significantly higher mean methylation rates than non-smokers at baseline. In male smokers, mean methylation levels decreased significantly during the cessation period.ConclusionOur findings replicate the findings of previous studies that BDNF plasma levels are altered in smokers. Furthermore, BDNF expression and gene methylation are altered during the first 14 days of cessation. Our novel findings of dysregulated methylation patterns in exon IV of the BDNF gene further support the thesis that BDNF plays a role in nicotine dependence.https://www.frontiersin.org/articles/10.3389/fpsyt.2022.897801/fulltobacco dependenceaddiction - smokingaddictionepigeneticaddict behavior |
| spellingShingle | Kerim Abdelkhalek Mathias Rhein Maximilian Deest Vanessa Buchholz Stefan Bleich Ralf Lichtinghagen Benjamin Vyssoki Helge Frieling Marc Muschler Phileas Johannes Proskynitopoulos Alexander Glahn Dysregulated Methylation Patterns in Exon IV of the Brain-Derived Neurotrophic Factor (BDNF) Gene in Nicotine Dependence and Changes in BDNF Plasma Levels During Smoking Cessation Frontiers in Psychiatry tobacco dependence addiction - smoking addiction epigenetic addict behavior |
| title | Dysregulated Methylation Patterns in Exon IV of the Brain-Derived Neurotrophic Factor (BDNF) Gene in Nicotine Dependence and Changes in BDNF Plasma Levels During Smoking Cessation |
| title_full | Dysregulated Methylation Patterns in Exon IV of the Brain-Derived Neurotrophic Factor (BDNF) Gene in Nicotine Dependence and Changes in BDNF Plasma Levels During Smoking Cessation |
| title_fullStr | Dysregulated Methylation Patterns in Exon IV of the Brain-Derived Neurotrophic Factor (BDNF) Gene in Nicotine Dependence and Changes in BDNF Plasma Levels During Smoking Cessation |
| title_full_unstemmed | Dysregulated Methylation Patterns in Exon IV of the Brain-Derived Neurotrophic Factor (BDNF) Gene in Nicotine Dependence and Changes in BDNF Plasma Levels During Smoking Cessation |
| title_short | Dysregulated Methylation Patterns in Exon IV of the Brain-Derived Neurotrophic Factor (BDNF) Gene in Nicotine Dependence and Changes in BDNF Plasma Levels During Smoking Cessation |
| title_sort | dysregulated methylation patterns in exon iv of the brain derived neurotrophic factor bdnf gene in nicotine dependence and changes in bdnf plasma levels during smoking cessation |
| topic | tobacco dependence addiction - smoking addiction epigenetic addict behavior |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2022.897801/full |
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