Early life stress and voluntary alcohol consumption in relation to Maoa methylation in male rats

Bendre, Megha; Granholm, Linnea; Drennan, Ryan; Meyer, Ann; Yan, Liying; Nilsson, Kent W.; Nylander, Ingrid; Comasco, Erika

doi:10.1016/j.alcohol.2018.11.001

Cited by 14 publications

(7 citation statements)

References 71 publications

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“…Within the 5'-upstream, smaller differences (1 -5%) were in fact observed for the majority of the analyzed CpGs. In the same region, small-in-magnitude hypermethylation of CpG −42 was previously observed in the promoter region of Monoamine Oxidase A (Maoa) of MS360E rats compared to MS15E as well as MS360W 48 , along with lower Maoa expression of MS360E rats compared to the same groups 38 . MAOA metabolizes monoamine neurotransmitters such as dopamine and serotonine and has been constantly implicated in behavioral regulation, stress-and alcohol-related phenotypes 49 .…”

Section: Discussionmentioning

confidence: 52%

DNA methylation of Vesicular Glutamate Transporters in the mesocorticolimbic brain following early life stress and ethanol exposure in adulthood

Vrettou

Yan²,

Nilsson

et al. 2021

Preprint

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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.

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Section: Discussionmentioning

confidence: 52%

DNA methylation of Vesicular Glutamate Transporters in the mesocorticolimbic brain following early life stress and ethanol exposure in adulthood

Vrettou

Yan²,

Nilsson

et al. 2021

Preprint

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“…Within the 5’-upstream, smaller differences (1–5%) were in fact observed for the majority of the analyzed CpGs. In the same region, and comparing the same groups (MS360E vs. MS15E and MS360W), small-in-magnitude hypermethylation of CpG − 42 was previously observed in the promoter region of Monoamine Oxidase A ( Maoa ) 53 , along with lower Maoa expression 41 . MAOA metabolizes monoamine neurotransmitters such as dopamine and serotonine and has been constantly implicated in behavioral regulation, stress- and alcohol-related phenotypes 54 .…”

Section: Discussionmentioning

confidence: 69%

DNA methylation of Vesicular Glutamate Transporters in the mesocorticolimbic brain following early-life stress and adult ethanol exposure—an explorative study

Vrettou

Yan²,

Nilsson

et al. 2021

Sci Rep

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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 exposure to ELS or ethanol. 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.

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“…An overview of the experimental timeline can be seen in Figure 1A, and a detailed description of the methods can be found in Comasco et al (2015) regarding the MS procedure and in Meyerson et al (2006) and Roman and Colombo (2009) for the MCSF procedure. Previously published results from the animal cohort (developmental body weights, voluntary ethanol consumption, and later genetic and epigenetic results) can be found in Bendre et al (2015Bendre et al ( , 2018, Comasco et al (2015); Nylander et al (2016), Todkar et al (2016); Granholm et al (2017), and Vrettou et al (2017).…”

Section: Methodsmentioning

confidence: 92%

Behavioral Profiling in Early Adolescence and Early Adulthood of Male Wistar Rats After Short and Prolonged Maternal Separation

Lundberg

Nylander

Roman

2020

Front. Behav. Neurosci.

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Early-life stress and its possible correlations to genes, environment, and later health outcomes can only be studied retrospectively in humans. Animal models enable the exploration of such connections with prospective, well-controlled study designs. However, with the recent awareness of replicability issues in preclinical research, the reproducibility of results from animal models has been highlighted. The present study aims to reproduce the behavioral effects of maternal separation (MS) previously observed in the multivariate concentric square field TM (MCSF) test. A second objective was to replicate the adolescent behavioral profiles previously described in the MCSF test. Male rats, subjected to short or prolonged MS or standard rearing, were subjected to behavioral testing in early adolescence and early adulthood. As seen in previous studies, the behavioral effects of MS in the MCSF were small at both tested time points. When tested in early adolescence, the animals exhibited a similar behavioral profile as previously seen, and the finding of adolescent behavioral types was also reproduced. The distribution of animals into the behavioral types was different than in the initial study, but in a manner consistent with developmental theories, as the current cohort was younger than the previous. Notably, the Shelter seeker behavioral type persisted through development, while the Explorer type did not. The lack of basal behavioral effect after MS is in line with the literature on this MS paradigm; the working hypothesis is that the prolonged MS gives rise to a phenotype predisposed to negative health outcomes but which is not apparent without additional provocation.

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Early life stress and voluntary alcohol consumption in relation to Maoa methylation in male rats

Cited by 14 publications

References 71 publications

DNA methylation of Vesicular Glutamate Transporters in the mesocorticolimbic brain following early life stress and ethanol exposure in adulthood

DNA methylation of Vesicular Glutamate Transporters in the mesocorticolimbic brain following early life stress and ethanol exposure in adulthood

DNA methylation of Vesicular Glutamate Transporters in the mesocorticolimbic brain following early-life stress and adult ethanol exposure—an explorative study

Behavioral Profiling in Early Adolescence and Early Adulthood of Male Wistar Rats After Short and Prolonged Maternal Separation

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