Adolescent Chronic Sleep Disruption Increases Blood-Brain Barrier Permeability, but in a Time-, Region- and Sex-Dependent Manner in CD-1 Mice.

Abstract

During puberty and adolescence, there is a natural change in the circadian rhythm, which could result in inadequate sleep and increase the likelihood of physical and mental health issues. Previously, we have developed a mouse model showing that adolescent chronic sleep disruption (CSD) induces depression-like behaviour in male and female CD-1 mice. However, the mechanisms underlying this effect are unknown. The current study investigates blood-brain barrier (BBB) permeability as a possible mechanism through which CSD may impact the brains of male and female CD-1 mice. At 6 weeks old, mice underwent either CSD for seven consecutive days or were left undisturbed. Mice were euthanized at either 24 h, 72 h, or 7 days following the last sleep disruption. BBB permeability was assessed in the whole brain and in specific brain regions (prefrontal cortex, hippocampus and hypothalamus). Results showed that at 72 h post-CSD, sleep-disrupted females had greater BBB permeability in the prefrontal cortex and hippocampus than non-sleep-disrupted females and sleep-disrupted males. At 7 days post-CSD, sleep-disrupted male and female mice displayed higher BBB permeability in the hypothalamus than non-sleep-disrupted mice. These findings demonstrate that CSD increases BBB permeability in a sex-, time- and brain region-dependent manner and females may be particularly vulnerable to the effects of CSD during adolescence. Understanding the factors disrupting BBB integrity will broaden our understanding of the impact of adolescent stress on brain function and behaviour.