Linking Sleep Deprivation to Neuronal Injury: A Review of Microglial and Glia-Mediated Mechanisms

Authors

Keywords:

neuronal loss, microglia, oxidative stress and excitotoxicity, inflammation, neurodegeneration, Sleep deprivation

Abstract

Introduction: Sleep deprivation is rapidly emerging as a critical factor in accelerating neurodegeneration, as it is becoming recognized as a key cause of cognitive decline and neurodegeneration. This review examines the complex relationship between prolonged wakefulness, microglial activation, and neuronal injury. It discusses the central role of glial-mediated immune responses in sleep-deprived brain pathology, drawing on various research studies. Methods: A comprehensive literature review was conducted using PubMed, Scopus, and Google Scholar. Peer-reviewed, open-access articles published in English from 2011 to 2022 were included. The review examines how the pathways of inflammation, oxidative stress and excitotoxicity are mediated by microglia in stress, culminating in synaptic and neuronal loss. Some of the various triggers to microglial dysfunction are discussed, including TREM2-dependent impairment of Amyloid-beta clearance and the impact of CRH-mediated HPA axis activation. Furthermore, the cross-talk between astrocytes and microglia highlights how glial overload contributes to lysosomal dysfunction and chronic inflammation. Results: The review identified strong evidence linking sleep deprivation to heightened microglial activation, increased pro-inflammatory cytokine release, and oxidative stress, all contributing to neuronal and synaptic loss. Studies showed that disrupted TREM2 signaling impairs Amyloid-beta clearance, while HPA axis overactivation intensifies microglial-mediated neuroinflammation. Cross-talk between astrocytes and microglia under prolonged wakefulness was found to exacerbate lysosomal dysfunction and chronic inflammation. These findings were particularly pronounced in models of Alzheimer’s disease, where sleep loss accelerated amyloid deposition and tau pathology. Experimental interventions targeting glial modulation and glymphatic function demonstrated potential neuroprotective effects. Discussion: The findings highlight the pivotal role of microglial dysfunction in the neuropathological consequences of sleep deprivation. Chronic sleep loss activates glial-mediated immune responses, disrupts clearance mechanisms, and fosters a neuroinflammatory environment conducive to synaptic degradation and neuronal injury. These mechanisms are particularly relevant in neurodegenerative diseases such as Alzheimer’s, where impaired glial regulation correlates with accelerated plaque accumulation and tau pathology. Conclusion: This review underscores sleep deprivation as a modifiable risk factor for neurodegeneration, primarily through glial dysregulation. Targeting microglial and astrocytic pathways, enhancing glymphatic clearance, and reducing oxidative stress may offer promising neuroprotective strategies. Further translational research is essential to develop clinically viable interventions.

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Published

2025-07-05

How to Cite

Maliyil, J. J., & Tatishvili, S. (2025). Linking Sleep Deprivation to Neuronal Injury: A Review of Microglial and Glia-Mediated Mechanisms. Health Policy, Economics and Sociology, 9(2). Retrieved from https://heconomic.cu.edu.ge/index.php/healthecosoc/article/view/9224

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