Circadian Control of Glial Cell Homeodynamics

Abstract

The molecular mechanisms that maintain circadian rhythms in mammalian as well as non-mammalian systems are well documented in neuronal populations but comparatively understudied in glia. Glia are highly dynamic in form and function, and the circadian clock provides broad dynamic ranges for the maintenance of this homeostasis, thus glia are key to understanding the role of circadian biology in brain function. Here, we highlight the implications of the molecular circadian clock on the homeodynamic nature of glia, underscoring the current gap in understanding the role of the circadian system in oligodendroglia lineage cells and subsequent myelination. Through this perspective, we will focus on the intersection of circadian and glial biology and how it interfaces with global circadian rhythm maintenance associated with normative and aberrant brain function.

Circadian Biology and the Neurovascular Unit

“…function although these areas of research have yet to be fully explored. 117,118 Although there is minimal direct data, it is easy to speculate that circadian rhythms in glia could have substantial impact on NVU function. Inflammatory oscillation in astrocytes, microglia, and OPCs could influence local levels of nitric oxide (NO) and vasoactive cytokines, as well as influence vessel reactivity.…”

“…87 Current research suggests that there may be circadian regulation of OPC differentiation, lipid synthesis, and mitochondrial function although these areas of research have yet to be fully explored. 117,118…”

Development of circadian neurovascular function and its implications

“…Circadian fluctuations in astrocyte structure and function throughout the brain are well documented ( McKee et al, 2020 ; Naseri Kouzehgarani et al, 2022 ; Rojo et al, 2022 ; Hastings et al, 2023 ). Astrocytes contribute to cell–cell coupling in the SCN, undergo daily changes in GFAP distribution and structural complexity, and physical coverage of neurons.…”

“…Astrocytes contribute to cell–cell coupling in the SCN, undergo daily changes in GFAP distribution and structural complexity, and physical coverage of neurons. Glia respond to daily oscillations in neuronal activity ( McKee et al, 2020 , Naseri Kouzehgarani et al, 2022 , Rojo et al, 2022 , Hastings et al, 2023 ). They may also be involved in thermoregulation, hormonal secretion, and sleep ( McKee et al, 2020 ).…”