Kushikata T, Kubota T, Fang J, Krueger J M
Department of Veterinary and Comparative Anatomy, Washington State University, Pullman, WA 99164-6520, USA.
Am J Physiol Regul Integr Comp Physiol. 2001 Apr;280(4):R1001-6. doi: 10.1152/ajpregu.2001.280.4.R1001.
Various growth factors (e.g., growth hormone-releasing hormone, acidic fibroblast growth factor, nerve growth factor, brain-derived neurotrophic factor, and interleukin-1) are implicated in sleep regulation. It is hypothesized that neuronal activity enhances the production of such growth factors, and they in turn form part of the sleep regulatory mechanism. Glial cell line-derived neurotrophic factor (GDNF) promotes development, differentiation, maintenance, and regeneration of neurons, and its production is induced by well-characterized sleep regulatory substances such as interleukin-1 and tumor necrosis factor. Therefore, we investigated whether GDNF would promote sleep. Twenty-six male Sprague-Dawley rats and 30 male New Zealand White rabbits were surgically implanted with electroencephalogram (EEG) and electromyogram (EMG; rats only) electrodes, a brain thermistor, and a lateral intracerebroventricular cannula. The animals were injected intracerebroventricularly with pyrogen-free saline and on a separate day with one of the following doses of GDNF: 5, 50, and 500 ng in rabbits and 50 and 500 ng in rats. The EEG, brain temperature, EMG (in rats), and motor activity (in rabbits) were recorded for 23 h after the intracerebroventricular injection. GDNF (500-ng dose) increased the time spent in nonrapid eye movement sleep in both rats and rabbits. Rapid eye movement sleep was not affected by the lower doses of GDNF but was inhibited in rabbits after the high dose. EEG slow-wave activity was not affected by GDNF. The current results provide further evidence that various growth factors are involved in sleep regulation.
多种生长因子（如生长激素释放激素、酸性成纤维细胞生长因子、神经生长因子、脑源性神经营养因子和白细胞介素-1）与睡眠调节有关。据推测，神经元活动会增强此类生长因子的产生，而它们反过来又构成睡眠调节机制的一部分。胶质细胞系源性神经营养因子（GDNF）促进神经元的发育、分化、维持和再生，其产生由白细胞介素-1和肿瘤坏死因子等特征明确的睡眠调节物质诱导。因此，我们研究了GDNF是否会促进睡眠。对26只雄性斯普拉格-道利大鼠和30只雄性新西兰白兔进行手术，植入脑电图（EEG）和肌电图（仅大鼠）电极、脑热敏电阻和侧脑室插管。给动物脑室内注射无热原盐水，并在另一天注射以下剂量之一的GDNF：兔注射5、50和500 ng，大鼠注射50和500 ng。在脑室内注射后记录23小时的脑电图、脑温、肌电图（大鼠）和运动活动（兔）。GDNF（500 ng剂量）增加了大鼠和兔非快速眼动睡眠的时间。较低剂量的GDNF对快速眼动睡眠没有影响，但高剂量后兔的快速眼动睡眠受到抑制。脑电图慢波活动不受GDNF影响。目前的结果进一步证明各种生长因子参与睡眠调节。
