Sleep and Risk of Multiple Sclerosis: Bridging the Gap Between Inflammation and Neurodegeneration via Glymphatic Failure

Sleep and Risk of Multiple Sclerosis: Bridging the Gap Between Inflammation and Neurodegeneration via Glymphatic Failure

Epidemiological studies identified insufficient and poor-quality sleep as independent risk factors for multiple sclerosis (MS). The glymphatic system, active during slow-wave sleep, clears brain waste through perivascular astrocytic aquaporin-4 (AQP4) channels. The presence of antigens induces a tra...

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Bibliographic Details
Main Authors: Mariateresa Buongiorno, Carmen Tur, Darly Milena Giraldo, Natalia Cullell, Jerzy Krupinski, Roberta Lanzillo, Gonzalo Sánchez-Benavides
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Brain Sciences
Subjects:
multiple sclerosis
glymphatic system
sleep
inflammation
neurodegeneration
Online Access:https://www.mdpi.com/2076-3425/15/7/766
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Summary:Epidemiological studies identified insufficient and poor-quality sleep as independent risk factors for multiple sclerosis (MS). The glymphatic system, active during slow-wave sleep, clears brain waste through perivascular astrocytic aquaporin-4 (AQP4) channels. The presence of antigens induces a transient, physiological lowering of glymphatic flux as a first step of an inflammatory response. A possible hypothesis linking infection with the Epstein–Barr virus, a well identified causal step in MS, and the development of the disease is that mechanisms such as poor sleep or less functional AQP4 polymorphisms may sustain glymphatic flow reduction. Such chronic glymphatic reduction would trigger a vicious circle in which the persistence of antigens and an inflammatory response maintains glymphatic dysfunction. In addition, viral proteins that persist in demyelinated plaques can depolarize AQP4, further restricting waste elimination and sustaining local inflammation. This review examines the epidemiological evidence connecting sleep and MS risk, and the mechanistic findings showing how poor sleep and other glymphatic modulators heighten inflammatory signaling implicated in MS pathogenesis. Deepening knowledge of glymphatic functioning in MS could open new avenues for personalized prevention and therapy.
ISSN:2076-3425

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