Lipidome Alterations of Prefrontal Cortex and Hippocampus of Mice‐Induced Sleep Deprivation

Abstract Chronic sleep deprivation (SD) impairscognitive function and promotes neurodegenerative changes, particularly in thehippocampus and prefrontal cortex. Study investigates the biochemical andimmunological effects of SD and evaluates the neuroprotective properties ofmelatonin using Fourier Transform Raman (FT‐Raman) spectroscopy. Hippocampaland cortical tissues from four groups of micecontrol, melatonin‐treated, sleep‐deprived, and sleep‐deprived with melatoninwere analyzed. FT‐Ramanspectra revealed significant changes in C─H bending, C─C vibrations, amides, and lipids between control and SD groups. SD led to increased lipidperoxidation, especially in the hippocampus, while melatonin treatment reducedlipid peroxidation and amide levels. In the cortex, melatonin mitigatedbiochemical alterations associated with SD, such as elevated amides and lipids.Immunological assessments showed SD‐induced changes in T helper (Th) cellsubpopulations, including an increase in effector Th cells and a decrease innaive Th cells. Melatonin treatment normalized these changes. PrincipalComponent Analysis (PCA) indicated clear separation between control and SDsamples, with PC1 and PC2 explaining 95.58% of the variance. Classificationusing the GS‐kNN algorithm achieved prefrontal cortex (accuracies: 79.167%) andin the hippocampus (accuracies: 70.833%). These findings highlight SD‐inducedbiochemical and immunological alterations and suggest melatonin'sneuroprotective role in reducing oxidative stress and modulating immunedysfunction.