Melatonin reverses obesity-induced neurodegeneration through glymphatic restoration
Abstract
Obesity is character ized by both central and peripheral alterations, increasing the risk for neurological and metabolic disorders. Recent evidence indicate that obesity can disrupt the glymphatic system and impair the clearance of cerebrospinal fluid (CSF). This can lead to the build of neurotoxic molecules, potentially explaining obesity’s risk for neurodegeneration and cognitive decline. Given that glymphatic flow is tightly regulated by sleep, and that sleep disturbances are seen in obesity, melatonin emerges as a promising candidate to target glymphatic dysfunction in obesity. In both clinical and preclinical models, exogenous melatonin improves sleep quality and enhances slow-wave sleep, which is the sleep stage when glymphatic clearance is most active. This perspective aims to explore the mechanistic links between obesity and glymphatic dysfunction, highlighting melatonin as a novel therapeutic to mitigate cognitive and neurological consequences associated with obesity through the restoration of the glymphatic system. The mechanistic studies are predominantly based on animal models; therefore, additional human studies that explore the effect of melatonin on glymphatic function are much needed. Glymphatic dysfunction as a consequence of obesity: Obesity is associated with increased risk of developing cognitive decline and neurodegeneration; however, the exact mechanisms involved remain to be elucidated. By adopting a reductional approach that examines specific brain…
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