Explicit memory, anxiety and depressive like behavior in mice exposed to chronic intermittent hypoxia, sleep fragmentation, or both during the daylight period

Cognitive Impairments, Neuroinflammation and Blood Brain Barrier Permeability in Mice Exposed to Chronic Sleep Fragmentation During the Daylight Period.

“…Sleep is a fundamental physiological function involved in the restoration of cellular and organ homeostasis and is essential for optimal daytime functioning [28,29]. Voluntary or imposed sleep deprivation or restriction has been extensively associated with neurobehavioral and cognitive deficits [22,50,58,[65][66][67], and several studies have suggested that such sleep deficits lead to BBB dysfunction and activation of inflammatory processes within the CNS, as illustrated by increased levels of proinflammatory cytokines and microglial activation [38,41,[68][69][70][71].…”

“…These processes can persist and even be amplified in a positive feedback loop, whereby microglia activation leading to increased inflammation and BBB disruption in turn leads to propagation and expansion of microglia activation [73,74]. Once the BBB is compromised, immune cells and potentially harmful substances such as toxins and pathogens can enter the brain, leading to incremental inflammation and brain cellular damage and apoptosis, a phenomenon that pertains to many neurodegenerative disorders such as Alzheimer disease and Parkinson disease [21,24,45,[75][76][77] We have previously shown that chronic SF mimicking the sleep disruption that characterizes moderate to severe patients with OSA induces increased oxidative stress in the brain that culminates in cognitive and behavioral deficits in mice [41,50,55,78]. Furthermore, subsequent studies further indicated that SF exposures induced increases in TNF-α levels in CNS which were critically involved in the increased sleep propensity that accompanies SF despite the absence of sleep deprivation in this experimental paradigm [41].…”

“…The SF device used to induce sleep disruption has been extensively described in previous studies [41,50,52,55,57,58]. Briefly, mice were housed in custom-designed cages containing an automatic horizontal bar sweeping immediately above the cage floor from one side to the other side of the cage.…”

“…The NOR test has been previously extensively described [50,58]. Briefly, this experimental paradigm is used to evaluate explicit memory based on the innate tendency for mice to explore novelty settings.…”

“…OSA has been closely linked to cognitive dysfunction, including impaired attention, memory, and executive functioning [4,[10][11][12]48,49]. In this setting, murine experiments employing either IH or SF have clearly demonstrated that these hallmarks of OSA can impair both declarative memory (memory for facts and events) and procedural memory (memory for skills and habits) [50][51][52][53][54][55][56]. Thus, a potential mechanism underlying the relationship between SF and cognitive dysfunction may involve the disruption of the BBB.…”