Stress-Induced Sleep Dysregulation: The Roles of Astrocytes and Microglia in Neurodegenerative and Psychiatric Disorders.

Stress and sleep share a reciprocal relationship, where chronic stress often leads to sleep disturbances that worsen neurodegenerative and psychiatric conditions. Non-neuronal cells, particularly astrocytes and microglia, play critical roles in the brain's response to stress and the regulation of sleep. Astrocytes influence sleep architecture by regulating adenosine signaling and glymphatic clearance, both of which can be disrupted by chronic stress, leading to reduced restorative sleep. Microglia, activated under stress conditions, drive neuroinflammatory processes that further impair sleep and exacerbate brain dysfunction. Additionally, the gut-brain axis mediates interactions between stress, sleep, and inflammation, with microbial metabolites influencing neural pathways. Many of these effects converge on the disruption of synaptic processes, such as neurotransmitter balance, synaptic plasticity, and pruning, which in turn contribute to the pathophysiology of neurodegenerative and psychiatric disorders. This review explores how these cellular and systemic mechanisms contribute to stress-induced sleep disturbances and their implications for neurodegenerative and psychiatric disorders, offering insights into potential therapeutic strategies targeting non-neuronal cells and the gut-brain axis.