Background Sleep restriction (SR) is recognized to alter neuroendocrine and immune parameters, yet whether these changes reflect overall alterations in signal magnitude or temporal shifts in systemic dynamics remains poorly defined. We evaluated the effects of subchronic sleep restriction on the 24-h diurnal profiles of serum corticosterone (CS), total white blood cell (WBC) counts, and granulocyte-enriched proportions in mice. Methods Male C57BL/6 mice were subjected to subchronic sleep restriction using the multiple-platform procedure or maintained under control conditions. Serum CS, total circulating WBC counts defined by FSC/SSC gating, and granulocyte-enriched percentages were measured across distinct Zeitgeber times and analyzed using two-way ANOVA with Holm corrections for multiple testing. Results Daily mean corticosterone levels and total WBC counts did not differ significantly between groups. A significant treatment × time interaction occurred for serum CS (p < 0.001), but time-point differences lost significance after Holm correction (p ≥ 0.06). Total WBC counts showed a borderline interaction (p = 0.050) with no time-point differences post-correction ≥, and CS–WBC correlations were not significant (p > 0.05). Conversely, granulocyte-enriched percentages exhibited a significant interaction (p = 0.002) and retained significant group differences post-correction at ZT5 (36.07 ± 2.57% vs. 18.10 ± 5.59%, adjusted p = 0.005) and ZT11 (53.03 ± 0.21% vs. 84.86 ± 8.64, adjusted p = 0.006). Conclusions The multiple-platform procedure is associated with time-specific differences in serum CS and granulocyte-enriched percentages without altering the diurnal mean CS or total WBC counts. Lacking direct mechanistic measurements, these data reflect potential temporal variations under sleep restriction paradigms rather than established corticosterone-mediated regulation, clock disruption, or altered tissue homing.
Alzheimer's disease is associated with disruptions in circadian rhythmicity, yet the underlying mechanisms remain only partially understood. Developing insights suggest that astrocytes possess their own intrinsic circadian clocks, influencing multiple functions in brain homeostasis. Given the central role of astrocytes in brain waste clearance, this review investigates how the astrocytic clock mediates brain waste clearance and contributes to Alzheimer's disease pathology. By reviewing recent findings on extracellular clearance, cellular protein homeostasis, cellular detoxification/redox defence and neurotransmitter homeostasis, this review bridges research on astrocytic clock disruption with altered brain waste clearance dynamics. It further highlights the relevance of these alterations to Alzheimer's disease pathology. Interestingly, some clock-gene disruptions are associated with markers suggestive of increased autophagic activity and glymphatic-related gene expression, which may represent a compensatory response to circadian clock alteration. However, whether these changes translate into improved functional clearance in vivo, and whether they meaningfully affect Alzheimer's disease progression, remains uncertain. In contrast, similar clock-gene alterations generally impair blood-brain barrier integrity, glutamate clearance and antioxidant response, decreasing waste clearance capacity. These findings suggest a possible bidirectional relationship, in which some pathways may partially compensate for impairments in others. However, it remains unclear to what extent an imbalance in these pathways contributes to the development and/or progression of Alzheimer's disease. Altogether, the astrocytic circadian clock is positioned as an important regulator of brain waste clearance and warrants future mechanistic and therapeutic investigation.
Retinal ganglion cells (RGCs) exhibit marked heterogeneity in their susceptibility to injury and disease. Intrinsically photosensitive retinal ganglion cells (ipRGCs), a small subset of melanopsin-expressing RGCs involved in non-image-forming visual functions, have emerged as a particularly informative example. In multiple experimental models, ipRGCs show relative resistance to acute insults such as optic nerve injury, excitotoxicity, and mitochondrial dysfuinction. In contrast, functional alterations and degeneration have been reported in aging and in neurodegenerative conditions including Alzheimer's and Parkinson's disease.This apparent discrepancy suggests that ipRGC survival may depend on the nature and duration of the underlying stress. In this review, we summarize current evidence on ipRGC resilience and vulnerability across a range of experimental and pathological contexts. We discuss candidate mechanisms that may contribute to these responses, including sustained activity, calcium handling, metabolic specialization, neurochemical interactions, and gene expression programs. We also consider the role of subtype-specific diversity within the ipRGC population in shaping these outcomes.Finally, we examine the potential of ipRGCs as biomarkers of disease and as a source of insight for neuroprotective strategies. Together, these observations support the view that ipRGC behaviour reflects an interaction between intrinsic cellular properties and the context in which they are engaged.
Chronic insufficient sleep is highly prevalent and is linked to an elevated risk of adverse health outcomes. Animal studies show that chronic sleep restriction, inducing a cumulative sleep debt, promotes blood-brain barrier (BBB) dysfunction, neuroinflammation, and can insidiously lead to neuropathology. Available studies primarily show diurnal or time-of-day variation in BBB permeability rather than direct manipulation of sleep state. Therefore, our fundamental understanding of BBB dynamics during the sleep-wake cycle remains limited. Investigating dynamic changes in the BBB induced by prolonged wakefulness is critical for understanding the heightened vulnerability of the brain to neurodegenerative diseases. In this review, we first discuss the potential role of sleep to modulate BBB dynamics. We then examine the known mechanisms driving BBB changes during sleep loss across different experimental paradigms and critically discuss the bidirectional interplay between sleep and the BBB, emphasizing how disruption of one system affects the other. This narrative-based review challenges the prevailing view of the BBB as a static, whole-brain barrier, proposing instead that it is a dynamic and adaptive interface whose regulation is tightly coupled to neuronal demands across the sleep-wake cycle.
