Department Integrative Physiology and Neurobiology, College of Veterinary Medicine, Washington State University, Spokane, Washington.
School of Medicine University of Washington, Spokane, Washington.
J Appl Physiol (1985). 2019 Sep 1;127(3):770-780. doi: 10.1152/japplphysiol.00366.2019. Epub 2019 Jul 11.
Interleukin-1β (IL1) is a sleep regulatory substance. The IL1/IL1 type 1 receptor complex requires a receptor accessory protein (AcP) to signal. There are three isoforms of AcP. In the current experiments, mice lacking a neuron-specific isoform, called AcPb knockout (AcPb KO), or mice lacking AcP + AcPb isoforms (AcP KO) or wild-type (WT) mice were used. Spontaneous sleep and sleep responses to sleep deprivation (SD) between zeitgeber time (ZT) 20-ZT4 and ZT8-ZT16 were characterized. Furthermore, somatosensory cortical protein extracts were examined for phosphorylated (p) proto-oncogene tyrosine-protein kinase sarcoma (Src) and p38MAPK levels at ZT4 and ZT16 and after SD. Spontaneous sleep was similar in the three strains, except rapid eye movement sleep (REMS) duration between ZT12-ZT16 was greater in AcP KO than WT mice. After SD at ZT4, only WT mice had non-REMS (NREMS) rebounds. All mouse strains lacked an NREMS rebound after SD at ZT16. All strains after both SD periods had REMS rebounds. AcPb KO mice, but not AcP KO mice, had greater EEG delta wave (0.5-4 Hz) power during NREMS than WT mice. p-Src was very low at ZT16 but high at ZT4, whereas p-p38MAPK was low at ZT4 and high at ZT16. p-p38MAPK levels were not sensitive to SD. In contrast, p-Src levels were less after SD at the = 0.08 level of significance in the strains lacking AcPb. We conclude that AcPb is required for NREMS responses to sleep loss, but not for SD-induced EEG delta wave or REMS responses. Interleukin-1β (IL1), a well-characterized sleep regulatory substance, requires an IL1 receptor accessory protein (AcP); one of its isoforms is neuron-specific (called AcPb). We showed that in mice, AcPb is required for nonrapid eye movement sleep responses following 8 h of sleep loss ending 4 h after daybreak but did not affect rapid eye movement sleep rebound. Sleep loss reduced phosphorylation of proto-oncogene tyrosine-protein kinase sarcoma but not of the less sensitive p38MAPK, downstream IL1 signaling molecules.
白细胞介素-1β（IL1）是一种睡眠调节物质。IL1/IL1 型 1 受体复合物需要一种受体辅助蛋白（AcP）来发出信号。AcP 有三种同工型。在当前的实验中，使用了缺乏神经元特异性同工型的小鼠，称为 AcPb 敲除（AcPb KO），或缺乏 AcP+AcPb 同工型（AcP KO）或野生型（WT）小鼠。在 Zeitgeber 时间（ZT）20-ZT4 和 ZT8-ZT16 之间，对自发睡眠和睡眠剥夺（SD）的睡眠反应进行了特征描述。此外，在 ZT4 和 ZT16 以及 SD 后，检查了感觉皮层蛋白提取物中磷酸化（p）原癌基因酪氨酸蛋白激酶肉瘤（Src）和 p38MAPK 的水平。三种品系的自发睡眠相似，除了 AcP KO 小鼠在 ZT12-ZT16 之间的快速眼动睡眠（REMS）持续时间比 WT 小鼠长。在 ZT4 进行 SD 后，只有 WT 小鼠有非快速眼动睡眠（NREMS）反弹。在 ZT16 进行 SD 后，所有小鼠品系均无 NREMS 反弹。所有品系在两个 SD 期后均有 REMS 反弹。与 WT 小鼠相比，AcPb KO 小鼠而非 AcP KO 小鼠在 NREMS 期间的 EEG 德尔塔波（0.5-4 Hz）功率更大。p-Src 在 ZT16 时非常低，但在 ZT4 时很高，而 p-p38MAPK 在 ZT4 时较低，在 ZT16 时较高。p-p38MAPK 水平对 SD 不敏感。相比之下，在缺乏 AcPb 的品系中，SD 后 p-Src 水平在 0.08 水平上显著降低。我们得出结论，AcPb 是对睡眠剥夺后 NREMS 反应所必需的，但不是对 SD 诱导的 EEG 德尔塔波或 REMS 反应所必需的。白细胞介素-1β（IL1）是一种特征明确的睡眠调节物质，需要一种白细胞介素 1 受体辅助蛋白（AcP）；其同工型之一是神经元特异性的（称为 AcPb）。我们表明，在小鼠中，AcPb 是在睡眠剥夺 8 小时后结束后 4 小时的非快速眼动睡眠反应所必需的，但不影响快速眼动睡眠反弹。睡眠剥夺降低了原癌基因酪氨酸蛋白激酶肉瘤的磷酸化，但不降低不太敏感的 p38MAPK，这是 IL1 信号的下游分子。
