Suchergebnisse

Background: Alcohol exposure impairs brain development and leads to a range of behavioural and cognitive dysfunctions, termed as foetal alcohol spectrum disorders. Although different mechanisms have been proposed to participate in foetal alcohol spectrum disorders, the molecular insights of such effects are still uncertain. Using a mouse model of foetal alcohol spectrum disorder, we have previously shown that maternal binge-like alcohol drinking causes persistent effects on motor, cognitive and emotional-related behaviours associated with neuroimmune dysfunctions. Aims: In this study, we sought to evaluate whether the long-term behavioural alterations found in offspring with early exposure to alcohol are associated with epigenetic changes in the hippocampus and prefrontal cortex. Methods: Pregnant C57BL/6 female mice underwent a model procedure for binge alcohol drinking throughout both the gestation and lactation periods. Subsequently, adult offspring were assessed for their cognitive function in a reversal learning task and brain areas were extracted for epigenetic analyses. Results: The results demonstrated that early binge alcohol exposure induces long-term behavioural effects along with alterations in histone acetylation (histone H4 lysine 5 and histone H4 lysine 12) in the hippocampus and prefrontal cortex. The epigenetic effects were linked with an imbalance in histone acetyltransferase activity that was found to be increased in the prefrontal cortex of mice exposed to alcohol. Conclusions: In conclusion, our results reveal that maternal binge-like alcohol consumption induces persistent epigenetic modifications, effects that might be associated with the long-term cognitive and behavioural impairments observed in foetal alcohol spectrum disorder models. ; The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by grants from the European Union's Horizon 2020 research and innovation program 2014-2020 under Grant Agreement No 634143, Spanish Ministry of Economy, Innovation and Competitiveness (SAF2015-69187-R-FEDER; SAF2016-75347-R) and Spanish Ministry of Health (Retic-ISCIII-RD/12/0028/007 and RD/16/0017/0010-FEDER and Plan Nacional sobre Drogas #2014/020, #2015/010 and #2018/007). The Department of Experimental and Health Sciences (UPF) is a 'Unidad de Excelencia María de Maeztu' funded by the MINECO (ref. MDM-2014-0370).

Alcohol binge drinking is on the increase in the young adult population, and consumption during pregnancy can be deleterious for foetal development. Maternal alcohol consumption leads to a wide range of long-lasting morphological and behavioural deficiencies known as foetal alcohol spectrum disorders (FASD), associated with neurodevelopmental disabilities. We sought to test the effects of alcohol on neuroimmune system activation and its potential relation to alcohol-induced neurodevelopmental and persistent neurobehavioural effects in offspring after maternal alcohol binge drinking during the prenatal period or in combination with lactation. Pregnant C57BL/6 female mice underwent a procedure for alcohol binge drinking either during gestation or both the gestation and lactation periods. Adult male offspring were assessed for cognitive functions and motor coordination. Early alcohol exposure induced motor coordination impairments in the rotarod test. Object recognition memory was not affected by maternal alcohol binge drinking, but Y-maze performance was impaired in pre- and early postnatal alcohol-exposed mice. Behavioural effects were associated with an upregulation of pro-inflammatory signalling (Toll-like receptor 4, nuclear factor-kappa B p65, NOD-like receptor protein 3, caspase-1, and interleukin-1β), gliosis, neuronal cell death and a reduction in several structural myelin proteins (myelin-associated glycoprotein, myelin basic protein, myelin proteolipid protein and myelin regulatory factor) in both the prefrontal cortex and hippocampus of adult mice exposed to alcohol. Altogether, our results reveal that maternal binge-like alcohol consumption induces neuroinflammation and myelin damage in the brains of offspring and that such effects may underlie the persistent cognitive and behavioural impairments observed in FASD. ; This study was supported by grants from the European Union's Horizon 2020 research and innovation programme 2014-2020 under Grant Agreement No 634143, the Spanish Ministry of Economy, Innovation and Competitiveness (SAF2013-41761-R-FEDER; SAF2015-69187-RFEDER; SAF2016-75347-R; SAF2016-75966-R), the Spanish Ministry of Health (Retic-ISCIII-RD/12/0028/007 and RD/12/0028/0024- FEDER), the Plan Nacional sobre Drogas (#2014/020, #2014/010 and #2016/004) and the Generalitat de Catalunya (2014SGR34). R. Lopez-Arnau position was funded by an institutional programme of the Universitat de Barcelona in collaboration with the Obra Social of the Fundacio Bancaria La Caixa.