Long-term consequences of early life stress on noradrenergic neurons activation in male and female mice

Major depression is a psychiatric disease extremely widespread and the leading cause of disability worldwide. Child abuse, defined as physical, emotional and/or sexual abuse or neglect, is considered as one of the strongest predictors of depression and suicidal behaviors. While the role of the locus-coeruleus noradrenergic system (LC-NE) in the long term effect of early life stress induced depression has been demonstrated in male, its involvement in female is lacking. The aim of this project is to better understand the contribution of LC-NE circuits in early life stress-induced depression in a sex-dependent manner. Employing a mouse model of maternal separation coupled with a litter-poor environment, as a model of early life stress, we tested the anxio-depressif phenotype on male and female litters at adulthood. Immunohistochemical labeling of the early activation marker cFos enables us to reveal the activation state of LC-NE neurons. Our findings highlighted a distinctive activity pattern of LC-NE neurons in male and female mice displaying depressive-like behaviours. These results demonstrate a functional role of the LC-NE system, emphasizing its distinctive implication in early life adversity according to sex.