Circadian rhythm and sleep-wake systems share the dynamic extracellular synaptic milieu

Abstract

The mammalian circadian and sleep-wake systems are closely aligned through their coordinated regulation of daily activity patterns. Although they differ in their anatomical organization and physiological processes, they utilize overlapping regulatory mechanisms that include an assortment of proteins and molecules interacting within the extracellular space. These extracellular factors include proteases that interact with soluble proteins, membrane-attached receptors and the extracellular matrix; and cell adhesion molecules that can form complex scaffolds connecting adjacent neurons, astrocytes and their respective intracellular cytoskeletal elements. Astrocytes also participate in the dynamic regulation of both systems through modulating neuronal appositions, the extracellular space and/or through release of gliotransmitters that can further contribute to the extracellular signaling processes. Together, these extracellular elements create a system that integrates rapid neurotransmitter signaling across longer time scales and thereby adjust neuronal signaling to reflect the daily fluctuations fundamental to both systems. Here we review what is known about these extracellular processes, focusing specifically on areas of overlap between the two systems. We also highlight questions that still need to be addressed. Although we know many of the extracellular players, far more research is needed to understand the mechanisms through which they modulate the circadian and sleep-wake systems.

C3orf70 Is Involved in Neural and Neurobehavioral Development

“…IRX3 is highly expressed in the midbrain and hindbrain of vertebrates, including zebrafish (irx3), and is involved in neurogenesis [24,25,30]. The midbrain is involved in regulation of circadian behavior and behavioral responses related to motor function and emotion [27,28] [26,29], which we confirmed were disrupted in c3orf70-KO zebrafish. These findings suggest that C3orf70 may regulate neurogenesis and neurobehavioral development via interactions with coexpressed genes such as IRX3.…”

“…Because the midbrain region, where zebrafish c3orf70 orthologs are highly expressed, is one of the most important regions in controlling sleep-wake systems [26], we next compared the circadian behavior of c3orf70-WT and KO zebrafish by analyzing the distance moved and the time spent in movement during periods of light and dark ( Figure 6A). During the dark period (21:00-07:00), the cumulative time spent at medium levels of mobility was significantly longer for c3orf70-KO compared with WT zebrafish (Figure 6D), whereas the total distance moved, the cumulative duration at high mobility, and cumulative duration in the center zone of the well (i.e., relative inactivity) were not significantly different between the WT and KO zebrafish ( Figure 6B, 6C, and 6E).…”

Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis

“…Changes in mechanical tension affect circadian clocks in mammary glands of virgin mice[13]. Adhesion molecules and proteolytic enzymes can affect the environment of the cells, and it has been hypothesized they mediate circadian timing in the central nervous as they can sense rapid signaling events and transmit-transfer signals into broader changes in cell activity with the daily changes[55].…”

Midday Napping and Successful Aging in Older People Living in the Mediterranean Region: The Epidemiological Mediterranean Islands Study (MEDIS)

“…Sleep is usually regulated by two body systems, i.e., sleep/wake homeostasis and the circadian rhythm [32]. However, stimulants such as coffee, tea, energy and soft drinks, or even alcohol may interfere with the circadian rhythm [33].…”