Offspring Susceptibility of Developing Depressive-like Phenotypes and Metabolic Dysfunction Following Prenatal Alcohol Exposure and Juvenile Stress in a Mouse Model
Abstract
Prenatal alcohol exposure (PAE) is the leading preventable cause of adverse fetal outcomes. Individuals with PAE are susceptible to developing secondary deficits such as depression and metabolic disorders. These secondary deficits are variable, creating challenges for clinical research and identifying at-risk individuals. Juvenile stress has been proposed to contribute to this variation. We established pre-clinical mouse models of early, acute PAE and late-juvenile sub-chronic unpredictable mild stress (SUMS) to investigate the resulting depressive-like phenotypes and metabolic dysfunction in offspring. Behavioural testing revealed that PAE offspring were susceptible to multiple depressive-like phenotypes, whereas juvenile SUMS offspring displayed only a subset. Metabolic analyses revealed that both PAE and juvenile SUMS offspring were susceptible to metabolic dysfunction, with the greatest dysmetabolism observed in females. Overall, this study provides novel findings into variation of outcomes of PAE and juvenile SUMS, and robust models to further investigate the combination of PAE and juvenile SUMS.