Disturbing sleep in female adolescent mice does not increase vulnerability to depression triggers later in life

Poor sleep quality is a major issue for many adolescents and is associated with fatigue, poor academic performance, and depression. Adolescence is a crucial neurodevelopmental stage where multiple neuropsychiatric illnesses often emerge, suggesting increased central nervous system vulnerability, specifically at this age, which could be exacerbated by poor sleep. Studies on adolescent mice show that sleep deprivation or sleep disturbance (SD) induces structural and functional brain changes, indicating that SD affects the adolescent brain. The long-term consequences of such changes are poorly understood. We hypothesize that SD during adolescence increases vulnerability to future depression triggers in adulthood, such as social isolation or inflammation. To test this, female adolescent mice (post-natal day (P)36) were subjected to SD for seven days, 4 h per day during the light phase (zeitgeber time 2-6). We demonstrate that this SD protocol acutely leads to changes in the expression of Cx3Cr1, and Dnmt3b in the hippocampus and of Htr1a in the prefrontal cortex. To examine the long-term consequences of the SD protocol during adulthood (P77-84), the mice were then either exposed to single housing or received a single injection of lipopolysaccharide (LPS) to mimic known triggers of depression. Behavioral changes were examined using digital ventilated cages to track home-cage activity and the open field and tail suspension tests to assess anxiety- and despair-like behavior, respectively. In contrast to our hypothesis, we did not observe any changes in home-cage activity, anxiety- or despair-like behavior as a result of combining SD in adolescent female mice with a depression trigger in adulthood. We conclude that the adolescent brain is sensitive to SD, but SD during adolescence in mice does not lead to an exacerbated depression-like response to social isolation or inflammation during adulthood.