This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Erika Comasco
Uppsala University
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
DNA methylation and gene expression can be altered by early life stress (ELS) and/or ethanol consumption. The present study aimed to investigate whether DNA methylation of the Vesicular Glutamate Transporters (Vglut)1–3 is related to previously observed Vglut1-3 transcriptional differences in the ventral tegmental area (VTA), nucleus accumbens (Acb), dorsal striatum (dStr) and medial prefrontal cortex (mPFC) of adult rats exposed to ELS, modelled by maternal separation, and voluntary ethanol consumption. Targeted next-generation bisulfite sequencing was performed to identify the methylation levels on 61 5′-cytosine-phosphate-guanosine-3′ sites (CpGs) in potential regulatory regions of Vglut1, 53 for Vglut2, and 51 for Vglut3. In the VTA, ELS in ethanol-drinking rats was associated with Vglut1-2 CpG-specific hypomethylation, whereas bidirectional Vglut2 methylation differences at single CpGs were associated with ELS alone. Exposure to both ELS and ethanol, in the Acb, was associated with lower promoter and higher intronic Vglut3 methylation; and in the dStr, with higher and lower methylation in 26% and 43% of the analyzed Vglut1 CpGs, respectively. In the mPFC, lower Vglut2 methylation was observed upon ELS- or ethanol-only. The present findings suggest Vglut1-3 CpG-specific methylation signatures of ELS and ethanol drinking, underlying previously reported Vglut1-3 transcriptional differences in the mesocorticolimbic brain.
Keywords
Gene Expression, Ventral Tegmental Area, Nucleus Accumbens, Dorsal Striatum, Medial Prefrontal Cortex, Bisulfite Sequencing
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Competing interest reported. : LY is key shareholder of EpigenDx; all genetic analyses were performed in a blind manner. The other authors have no conflict of interest to declare.
This is a list of supplementary files associated with this preprint. Click to download.
- PaperIISupplementaryR120210224MV.docx
Supplementary Material
- Table1.png
Table 1. Correlations between CpG methylation and gene expression as well as blood corticosterone levels for Slc17a7/Vglut1 and Slc17a6/Vglut2 genes in the VTA by group. The color bar indicates the Spearman´s rho coefficient; * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 11 Mar, 2021
No community comments so far
Review #1 received
Received 05 Apr, 2021
Reviewer #1 agreed
On 19 Mar, 2021
Reviewer #2 agreed
On 19 Mar, 2021
Reviewer #3 agreed
On 19 Mar, 2021
Reviewers invited
Invitations sent on 19 Mar, 2021
Editor assigned
On 15 Mar, 2021
Editor invited
On 03 Mar, 2021
Submission checks complete
On 03 Mar, 2021
First submitted
On 26 Feb, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Erika Comasco
Uppsala University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 11 Mar, 2021
No community comments so far
Review #1 received
Received 05 Apr, 2021
Reviewer #1 agreed
On 19 Mar, 2021
Reviewer #2 agreed
On 19 Mar, 2021
Reviewer #3 agreed
On 19 Mar, 2021
Reviewers invited
Invitations sent on 19 Mar, 2021
Editor assigned
On 15 Mar, 2021
Editor invited
On 03 Mar, 2021
Submission checks complete
On 03 Mar, 2021
First submitted
On 26 Feb, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
DNA methylation and gene expression can be altered by early life stress (ELS) and/or ethanol consumption. The present study aimed to investigate whether DNA methylation of the Vesicular Glutamate Transporters (Vglut)1–3 is related to previously observed Vglut1-3 transcriptional differences in the ventral tegmental area (VTA), nucleus accumbens (Acb), dorsal striatum (dStr) and medial prefrontal cortex (mPFC) of adult rats exposed to ELS, modelled by maternal separation, and voluntary ethanol consumption. Targeted next-generation bisulfite sequencing was performed to identify the methylation levels on 61 5′-cytosine-phosphate-guanosine-3′ sites (CpGs) in potential regulatory regions of Vglut1, 53 for Vglut2, and 51 for Vglut3. In the VTA, ELS in ethanol-drinking rats was associated with Vglut1-2 CpG-specific hypomethylation, whereas bidirectional Vglut2 methylation differences at single CpGs were associated with ELS alone. Exposure to both ELS and ethanol, in the Acb, was associated with lower promoter and higher intronic Vglut3 methylation; and in the dStr, with higher and lower methylation in 26% and 43% of the analyzed Vglut1 CpGs, respectively. In the mPFC, lower Vglut2 methylation was observed upon ELS- or ethanol-only. The present findings suggest Vglut1-3 CpG-specific methylation signatures of ELS and ethanol drinking, underlying previously reported Vglut1-3 transcriptional differences in the mesocorticolimbic brain.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Loading...