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- Bendre, Megha, et al.
(författare)
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Early life stress and voluntary alcohol consumption in relation to Maoa methylation in male rats.
- 2019
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Ingår i: Alcohol. - : Elsevier BV. - 0741-8329 .- 1873-6823. ; 79, s. 7-16
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Tidskriftsartikel (refereegranskat)abstract
- Early life stress (ELS) or alcohol consumption can influence DNA methylation and affect gene expression. The monoamine oxidase A (Maoa) encodes the enzyme that metabolizes monoaminergic neurotransmitters crucial for the stress response, alcohol reward, and reinforcement. Previously, we reported lower Maoa expression in the nucleus accumbens and dorsal striatum of male rats exposed to ELS during the first three postnatal weeks, and to voluntary alcohol consumption in adulthood, compared with controls. The present study continued to investigate the effect of ELS and alcohol consumption on Maoa methylation, and its relation to Maoa expression in these animals. We selected candidate CpGs after performing next-generation bisulfite sequencing of the Maoa promoter, intron 1-5, exons 5 and 6, together comprised of 107 CpGs, in a subgroup of rats. Pyrosequencing was used to analyse the methylation of ten candidate CpGs in the promoter and intron 1 in the entire sample. ELS and alcohol displayed an interaction effect on CpG-specific methylation in the dorsal striatum. CpG-specific methylation correlated with Maoa expression, corticosterone levels, and alcohol consumption in a brain region-specific manner. CpG-specific methylation in the Maoa promoter was a potential moderator of the interaction of ELS with alcohol consumption on Maoa expression in the NAc. However, the findings were sparse, did not survive correction for multiple testing, and the magnitude of differences in methylation levels was small. In conclusion, CpG-specific Maoa methylation in the promoter and intron 1 may associate with ELS, alcohol consumption and Maoa expression in reward-related brain regions.
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- Comasco, Erika, et al.
(författare)
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Alpha 2a-Adrenoceptor Gene Expression and Early Life Stress-Mediated Propensity to Alcohol Drinking in Outbred Rats
- 2015
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 12:7, s. 7154-7171
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Tidskriftsartikel (refereegranskat)abstract
- Stressful events early in life, later high alcohol consumption and vulnerability to alcohol use disorder (AUD) are tightly linked. Norepinephrine is highly involved in the stress response and the alpha 2A-adrenoceptor, which is an important regulator of norepinephrine signalling, is a putative target in pharmacotherapy of AUD. The aim of the present study was to investigate the effects of early-life stress and adult voluntary alcohol drinking on the alpha 2A-adrenoceptor. The relative expression and promoter DNA methylation of the Adra2a gene were measured in the hypothalamus, a key brain region in stress regulation. A well-characterized animal model of early-life stress was used in combination with an episodic voluntary drinking in adulthood. Alcohol drinking rats with a history of early-life stress had lower Adra2a expression than drinking rats not exposed to stress. Alcohol intake and Adra2a gene expression were negatively correlated in high-drinking animals, which were predominantly rats subjected to early-life stress. The results provide support for a link between early-life stress, susceptibility for high alcohol consumption, and low Adra2a expression in the hypothalamus. These findings can increase our understanding of the neurobiological basis for vulnerability to initiate risk alcohol consumption and individual differences in the response to 2A-adrenoceptor agonists.
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