Porkka-Heiskanen T, Smith S E, Taira T, Urban J H, Levine J E, Turek F W, Stenberg D
Department of Physiology, University of Helsinki, Finland.
Am J Physiol. 1995 Jun;268(6 Pt 2):R1456-63. doi: 10.1152/ajpregu.1995.268.6.R1456.
Noradrenergic locus ceruleus neurons are most active during waking and least active during rapid eye movement (REM) sleep. We expected REM sleep deprivation (REMSD) to increase norepinephrine utilization and activate the tyrosine hydroxylase (TH) gene critical for norepinephrine production. Male Wistar rats were deprived of REM sleep with the platform method. Rats were decapitated after 8, 24, or 72 h on small (REMSD) or large (control) platforms or after 8 or 24 h of rebound sleep after 72 h of the platform treatment. During the first 24 h, norepinephrine concentration, measured by high-performance liquid chromatography/electrochemical detection, was lower in the neocortex, hippocampus, and posterior hypothalamus in REMSD rats than in large-platform controls. After 72 h of REMSD, TH mRNA, measured by in situ hybridization, was increased in the locus ceruleus and norepinephrine concentrations were increased. Polygraphy showed that small-platform treatment caused effective and selective REMSD. Serum corticosterone measurement by radioimmunoassay indicated that the differences found in norepinephrine and TH mRNA were not due to differences in stress between the treatments. The novel finding of sleep deprivation-specific increase in TH gene expression indicates an important mechanism of adjusting to sleep deprivation.
去甲肾上腺素能蓝斑神经元在清醒时最为活跃，在快速眼动（REM）睡眠时最不活跃。我们预期快速眼动睡眠剥夺（REMSD）会增加去甲肾上腺素的利用率，并激活对去甲肾上腺素产生至关重要的酪氨酸羟化酶（TH）基因。采用平台法剥夺雄性Wistar大鼠的快速眼动睡眠。在小平台（REMSD）或大平台（对照）上8、24或72小时后，或在平台处理72小时后的8或24小时反弹睡眠后，将大鼠断头。在最初的24小时内，通过高效液相色谱/电化学检测测量的去甲肾上腺素浓度，在REMSD大鼠的新皮层、海马体和下丘脑后部低于大平台对照组。REMSD 72小时后，通过原位杂交测量的TH mRNA在蓝斑中增加，去甲肾上腺素浓度也增加。多导睡眠图显示小平台处理导致有效且选择性的快速眼动睡眠剥夺。通过放射免疫测定血清皮质酮表明，去甲肾上腺素和TH mRNA的差异不是由于处理之间的应激差异。TH基因表达睡眠剥夺特异性增加这一新发现表明了一种适应睡眠剥夺的重要机制。
