Prenatal N-acetyl-cysteine administration moderates the long-term negative effects of maternal obesity in adolescent male and female mouse offspring

Obesity during pregnancy may affect offspring developmental trajectories representing a risk factor for mental health. Amongst the mechanisms called into question inflammation, oxidative stress and the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis appear as the most suitable. We investigated the emotional phenotype of male and female offspring of dams exposed to a high-fat diet (HFD, a mouse model of maternal obesity) before and during pregnancy. We also tested the efficacy of N-acetyl-cysteine (NAC – an antioxidant) in preventing the negative effects of HFD. We focused on adolescence, an age of main vulnerability for the onset of psychopathologies. Female C57BL/6N mice were fed HFD for 13 weeks and, after 5 weeks, were also exposed to NAC (1 g/kg b.w.) via drinking water, until delivery. Emotionality was assessed in 35-45-day-old adolescent mice by means of the elevated-plus-maze (EPM) and social interaction tests (SIT). A forced swimming test was used both to evaluate depressive-like behaviour as well as a stressful challenge to measure HPA axis reactivity. NAC was effective in moderating body weight gain in HFD-treated dams. Prenatal HFD reduced exploratory behaviours in the EPM in periadolescent offspring; NAC administration resulting in increased social interactions in the offspring of HFD dams. Analyses of depression-like behaviours, HPA axis functionality and brain transcriptomics are currently ongoing for mechanistic insight. Data from these studies indicate that the long-term effects of maternal obesity may be mediated by changes in oxidative stress and point to NAC as a potential preventive strategy. ERANET-NEURON-JTC 2018 (Mental Disorders) Project ‘‘EMBED”.