International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Japan Society for the Promotion of Science (JSPS) International Research Fellow, Tokyo 102-0083, Japan.
PhD Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Cell Rep. 2021 Aug 17;36(7):109558. doi: 10.1016/j.celrep.2021.109558.
Sleep is generally viewed as a period of recovery, but how the supply of cerebral blood flow (CBF) changes across sleep/wake states has remained unclear. Here, we directly observe red blood cells (RBCs) within capillaries, where the actual substance exchange between the blood and neurons/glia occurs, by two-photon microscopy. Across multiple cortical areas, average capillary CBF is largely increased during rapid eye movement (REM) sleep, whereas it does not differ between periods of active wakefulness and non-REM sleep. Capillary RBC flow during REM sleep is further elevated following REM sleep deprivation, suggesting that capillary CBF reflects REM sleep pressure. At the molecular level, signaling via adenosine A2a receptors is crucial; in A2a-KO mice, capillary CBF upsurge during REM sleep is dampened, and effects of REM sleep pressure are abolished. These results provide evidence regarding the dynamics of capillary CBF across sleep/wake states and insights to the underlying mechanisms.
睡眠通常被视为恢复的阶段，但睡眠/觉醒状态下脑血流（CBF）的供应如何变化仍不清楚。在这里，我们通过双光子显微镜直接观察到毛细血管内的红细胞（RBC），血液和神经元/神经胶质之间的实际物质交换就在这里发生。在多个皮质区域，平均毛细血管 CBF 在快速眼动（REM）睡眠期间大大增加，而在活跃的觉醒期和非快速眼动睡眠期间没有差异。在 REM 睡眠剥夺后，毛细血管 RBC 在 REM 睡眠期间的流动进一步升高，表明毛细血管 CBF 反映了 REM 睡眠压力。在分子水平上，通过腺苷 A2a 受体的信号传递至关重要；在 A2a-KO 小鼠中，REM 睡眠期间毛细血管 CBF 的激增减弱，而 REM 睡眠压力的作用被消除。这些结果提供了有关睡眠/觉醒状态下毛细血管 CBF 动态的证据，并深入了解了潜在的机制。
