Bai Lily, Sarkar Ramanuj, Lee Faith, Wu Joseph Chong-Sang, Vawter Marquis P
Hackensack Meridian School of Medicine, Nutley, NJ, USA.
Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, USA.
Complex Psychiatry. 2025 Mar 24;11(1):50-71. doi: 10.1159/000545461. eCollection 2025 Jan-Dec.
Sleep deprivation affects cognitive performance and immune function, yet its mechanisms and biomarkers remain unclear. This study explored the relationships among gene expression, brain metabolism, sleep deprivation, and sex differences.
Fluorodeoxyglucose-18 positron emission tomography measured brain metabolism in regions of interest, and RNA analysis of blood samples assessed gene expression pre- and post-sleep deprivation. Mixed model regression and principal component analysis identified significant genes and regional metabolic changes.
There were 23 and 28 differentially expressed probe sets for the main effects of sex and sleep deprivation, respectively, and 55 probe sets for their interaction (FDR-corrected < 0.05). Functional analysis of genes affected by sleep deprivation revealed pathway enrichment in nucleoplasm- and UBL conjugation-related genes. Genes with significant sex effects mapped to chromosomes Y and 19 (Benjamini-Hochberg FDR < 0.05), with 11 genes (4%) and 29 genes (10.5%) involved, respectively. Differential gene expression highlighted sex-based differences in innate and adaptive immunity. For brain metabolism, sleep deprivation resulted in significant decreases in the left insula, left medial prefrontal cortex (BA32), left somatosensory cortex (BA1/2), and left motor premotor cortex (BA6) and increases in the right inferior longitudinal fasciculus, right primary visual cortex (BA17), right amygdala, left cerebellum, and bilateral pons.
Sleep deprivation broadly impacts brain metabolism, gene expression, and immune function, revealing cellular stress responses and hemispheric vulnerability. These findings enhance our understanding of the molecular and functional effects of sleep deprivation.
睡眠剥夺会影响认知能力和免疫功能，但其机制和生物标志物仍不清楚。本研究探讨了基因表达、脑代谢、睡眠剥夺和性别差异之间的关系。
采用18氟脱氧葡萄糖正电子发射断层扫描测量感兴趣区域的脑代谢，并通过对血样进行RNA分析来评估睡眠剥夺前后的基因表达。混合模型回归和主成分分析确定了显著的基因和区域代谢变化。
性别和睡眠剥夺的主要效应分别有23个和28个差异表达的探针集，二者相互作用有55个探针集（错误发现率校正<0.05）。对受睡眠剥夺影响的基因进行功能分析，发现核质和泛素结合相关基因的通路富集。具有显著性别效应的基因定位于Y染色体和19号染色体（本雅明尼-霍赫贝格错误发现率<0.05），分别涉及11个基因（4%）和29个基因（10.5%）。差异基因表达突出了先天免疫和适应性免疫中基于性别的差异。对于脑代谢，睡眠剥夺导致左侧岛叶、左侧内侧前额叶皮质（BA32）、左侧躯体感觉皮质（BA1/2）和左侧运动前运动皮质（BA6）显著降低，右侧下纵束、右侧初级视觉皮质（BA17）、右侧杏仁核、左侧小脑和双侧脑桥增加。
睡眠剥夺广泛影响脑代谢、基因表达和免疫功能，揭示了细胞应激反应和半球易损性。这些发现增进了我们对睡眠剥夺的分子和功能效应的理解。
