Maternal alcohol binge drinking induces persistent neuroinflammation associated with myelin damage and behavioural dysfunctions in offspring mice

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