Backgrounds: Impaired sleep is independent risk factor of neurodegeneration and dementia. Chronic insomnia impairs melatonin (MEL) production that is directly proportionate to its duration. The underlying mechanisms linking sleep loss to dementia and the possible therapeutic effect of melatonin have not been fully elucidated. Previous research showed great controversy concerning the effects of paradoxical sleep deprivation (PSD) on body weight, serum lipoproteins, and inflammatory cytokines.

Goals: To examine the effect of chronic paradoxical sleep deprivation (PSD) with and without MEL supplementation on memory using RAWM, parameters of metabolic syndrome (MS), liver enzymes, serum cortisol, and inflammatory cytokines as well as liver, colon, and brain histopathology.

Methods: Forty rats were divided into four groups ten animals each; C: control, G: grid group, SD: sleep deprivation group, and SD+MEL sleep deprivation treated with melatonin.

Results: MEL supplementation reversed PSD-induced memory deficits (P<0.05), the elevation of serum cortisol (P<0.001), glucose (P<0.05), ALT (P<0.05), AST (P<0.001), TNF-alpha (P<0.001), IL-10 (P<0.01) and improved colon, liver, and brain architecture. Melatonin reduced body weight (P<0.05), total cholesterol, LDL-c, and triglycerides as well as increased HDL-c (P<0.001).

Conclusion: MEL has a protective effect against chronic PSD-induced metabolic malfunction and cognitive deterioration by reducing stress, improving immunity, and maintaining colonic wall integrity.