Sakai Keita, Ishikawa Akiyoshi, Mizuno Yuri, Maki Takehiro, Oda Yasuhiro, Takahashi Eiki
Sleep Science Laboratories, HAMRI Co., Ltd., Ibaraki, 306-0128, Japan.
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.
Heliyon. 2020 Mar 4;6(3):e03524. doi: 10.1016/j.heliyon.2020.e03524. eCollection 2020 Mar.
The most widely used animal models to develop sleep-disorder drugs are rodents, particularly rats and mice. However, unlike humans, these rodents are nocturnal. Thus, diurnal non-human primates represent a valuable and more translational animal model to study sleep. Although sleep-disorder drugs have been screened in non-human primates, the use of a telemetry system is not a desirable method for a rapid drug efficacy assessment system because of the need for expensive equipment, complicated surgery, and the long time before results can be obtained from analysis by inspection. Locomotor activity has traditionally been used as an indicator of the effects of drugs, genes, and disease models. The Nano-Tag, a new device for analyzing activity after an easy implantation surgery, measures locomotor activity without expensive equipment and the need for inspection for data processing, and the overall cost is much lower than that of a telemetry system. In this study, we compared the data obtained from polysomnography and on locomotor activity in telemetry transmitter-embedded cynomolgus monkeys by implanting the Nano-Tag subcutaneously in the forehead and administering sleep-disorder drugs to confirm if sleep-wake states could be measured using the Nano-Tag. When we compared the changes in awake time per unit time measured using polysomnography and locomotor activity counts per unit time measured using the Nano-Tag, cynomolgus monkeys exhibited a diurnal preference, and the correlation coefficients were positive during the 24-h period. Additionally, the correlation coefficients during the 12-h dark period were positive when the hypersomnia treatment drug modafinil was administered. The correlation coefficients during the 12-h light period were also positive when the insomnia treatment drug triazolam was administered. These results suggest that measuring locomotor activity is an effective tool for identifying sleep-wake states and screening sleep-disorder drugs at low cost and with less burden to animal subjects.
用于研发睡眠障碍药物的最广泛使用的动物模型是啮齿动物,尤其是大鼠和小鼠。然而,与人类不同,这些啮齿动物是夜行性的。因此,昼行性非人灵长类动物是研究睡眠的有价值且更具转化性的动物模型。尽管已经在非人灵长类动物中筛选了睡眠障碍药物,但由于需要昂贵的设备、复杂的手术以及从检查分析中获得结果所需的长时间,使用遥测系统对于快速药物疗效评估系统来说并不是一种理想的方法。传统上,运动活动一直被用作药物、基因和疾病模型效果的指标。Nano-Tag是一种新型设备,在简单的植入手术后即可分析活动,无需昂贵设备且无需检查进行数据处理来测量运动活动,总体成本远低于遥测系统。在本研究中,我们通过在前额皮下植入Nano-Tag并给食蟹猴施用睡眠障碍药物,比较了从多导睡眠图获得的数据以及植入遥测发射器的食蟹猴的运动活动数据,以确认是否可以使用Nano-Tag测量睡眠-觉醒状态。当我们比较使用多导睡眠图测量的每单位时间清醒时间的变化和使用Nano-Tag测量的每单位时间运动活动计数时,食蟹猴表现出昼行偏好,并且在24小时期间相关系数为正。此外,在施用治疗发作性睡病的药物莫达非尼时,12小时黑暗期的相关系数为正。在施用治疗失眠的药物三唑仑时,12小时光照期的相关系数也为正。这些结果表明,测量运动活动是一种低成本且对动物受试者负担较小的识别睡眠-觉醒状态和筛选睡眠障碍药物的有效工具。