English Erika L, Krueger James M
School of Molecular Biosciences, Washington State University, Pullman, WA, United States.
Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, United States.
Front Neurosci. 2025 Jul 16;19:1608302. doi: 10.3389/fnins.2025.1608302. eCollection 2025.
Sleep-inducing bacterial cell wall components isolated from brain and urine of sleep deprived animals were identified as peptidoglycan (PG) and muropeptides in the 1980s. Following host detection of PG/muropeptides, downstream signaling mechanisms include release of effector molecules, e.g., cytokines involved in sleep regulation. Understanding of physiological brain PG changes has remained limited, in part due to the historic difficulties of PG quantitation. Herein, we report murine brain PG levels in multiple brain areas within the context of animals' rest-wake cycles and after sleep loss. Significant time-of-day changes in brain PG levels occurred in all brain areas; lowest levels occurred during the transition from rest to wake periods, at zeitgeber time 12 (ZT12). Highest levels of PG were in brainstem while olfactory bulb, hypothalamic, and cortical PG levels were lower. After 3 h of sleep disruption, PG levels increased in the somatosensory cortex, but decreased in brainstem, and hypothalamus. After 6 h of sleep disruption, PG increased in the brainstem and olfactory bulb compared to control levels. Further, RNA-seq analyses of somatosensory cortical tissue was used to assess sleep loss-dependent changes in genes previously linked to PG. Multiple PG-related genes had altered expression with sleep loss including PG binding and signaling molecules, e.g., Pglyrp1 and Nfil3. In summary, brain PG levels were dependent on time of day, brain area, and sleep history. Further, sleep loss altered brain gene expression for PG-linked genes. Collectively, these data are consistent with the hypothesis that microbe-host symbiotic interactions are involved in murine sleep regulatory mechanisms.
20世纪80年代，从睡眠剥夺动物的大脑和尿液中分离出的诱导睡眠的细菌细胞壁成分被鉴定为肽聚糖（PG）和胞壁肽。宿主检测到PG/胞壁肽后，下游信号传导机制包括效应分子的释放，例如参与睡眠调节的细胞因子。对生理性脑PG变化的理解仍然有限，部分原因是PG定量在历史上存在困难。在此，我们报告了在动物的休息-觉醒周期背景下以及睡眠剥夺后多个脑区的小鼠脑PG水平。所有脑区的脑PG水平均出现显著的日变化；最低水平出现在从休息到觉醒期的过渡阶段，即授时因子时间12（ZT12）。PG水平最高的是脑干，而嗅球、下丘脑和皮质的PG水平较低。睡眠中断3小时后，体感皮质中的PG水平升高，但脑干和下丘脑中的PG水平降低。睡眠中断6小时后，与对照水平相比，脑干和嗅球中的PG升高。此外，利用体感皮质组织的RNA测序分析来评估先前与PG相关的基因在睡眠剥夺后的变化。多个与PG相关的基因在睡眠剥夺后表达发生改变，包括PG结合和信号分子，例如Pglyrp1和Nfil3。总之，脑PG水平取决于一天中的时间、脑区和睡眠史。此外，睡眠剥夺改变了与PG相关基因的脑基因表达。总体而言，这些数据与微生物-宿主共生相互作用参与小鼠睡眠调节机制的假说一致。
