Högskolan i Skövde

Sleep disruption is a modifiable risk factor for cognitive decline and neurodegeneration, with astrocytes and microglia playing a central role in this link. This systematic review synthesizes experimental evidence on how total, selective, or fragmented sleep deprivation alters glial function and how these changes relate to executive function, memory, and neuropathology. Following PRISMA 2020, I searched MEDLINE (EBSCO) and Scopus (2010–April 2025). Eligible in vivo or ex vivo studies employed defined sleep-loss protocols, validated glial markers (e.g., GFAP, AQP4, Iba1, CD68, cytokines), and assessed cognitive or neuropathological outcomes; the risk of bias was appraised using SYRCLE (animals) and RoB-2 (humans). Twenty-six studies met the criteria. Across paradigms, sleep loss increased microglial activation (TNF-α, IL-1β, IL-6; complement signaling), induced astrogliosis with AQP4 depolarization and enhanced astrocytic phagocytosis, and reduced synaptic proteins (PSD-95, synaptophysin), co-occurring with impaired spatial/recognition memory and, in Alzheimer’s models, greater Aβ deposition and tau phosphorylation. Emerging evidence suggests glymphatic clearance efficiency depends on vascular and arousal factors beyond sleep stage alone. These findings highlight promising therapeutic targets spanning sleep restoration and direct glial modulation: slow-wave augmentation (acoustic stimulation, noninvasive brain stimulation), circadian alignment (timed light, melatonin agonism), treatment of sleep disorders (CBT-I, dual orexin receptor antagonists, CPAP for OSA), and glial-pathway interventions (complement blockade [C1q/C3/C3aR], microglial modulation [P2X7, NLRP3, CX3CR1/TREM2], and restoration of astrocytic AQP4 polarity and endfeet integrity). Overall, sleep deprivation disrupts glial homeostasis and aligns with cognitive impairment and neurodegenerative pathology.