Kane Kelby M, Iradukunda Diane, McLouth Christopher J, Guo Landys Z, Wang Jun, Subramoniam Anjana, Huffman Dillon, Donohue Kevin D, O'Hara Bruce F, Sunderam Sridhar, Wang Qing Jun
Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, USA.
Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky, USA.
J Sleep Res. 2025 Aug;34(4):e14461. doi: 10.1111/jsr.14461. Epub 2025 Jan 28.
The neuronal ceroid lipofuscinoses (NCLs) are a group of recessively inherited neurodegenerative diseases characterizsed by lysosomal storage of fluorescent materials. CLN3 disease, or juvenile Batten disease, is the most common NCL that is caused by mutations in the Ceroid Lipofuscinosis, Neuronal 3 (CLN3) gene. Sleep disturbances are among the most common symptoms associated with CLN3 disease that deteriorate the patients' life quality, yet this is understudied and has not been delineated in animal models of the disease. The current study utilised PiezoSleep, a non-invasive, automated piezoelectric motion sensing system, to classify sleep and wakefulness in a Cln3 (Cln3KO) mouse model and age- and sex-matched wild-type (WT) controls. The sleep-wake classification by PiezoSleep was found to be about 90% accurate when validated against simultaneous polysomnographic recordings including electroencephalography (EEG) and electromyography (EMG) in a small cohort of WT and Cln3KO mice. Our large cohort PiezoSleep study revealed sleep abnormalities during the light period in male Cln3KO mice compared with WT male mice, and more subtle differences in Cln3KO female mice in the dark period compared with WT female mice. Our characterisation of sleep in the Cln3KO mouse model aligns with sleep abnormalities seen in CLN3 disease patients and serves as a basis to continue examining sleep disturbances commonly reported for CLN3 disease and other NCLs. As the first animal model study capturing sleep disturbances in CLN3 disease, our work will facilitate future studies into the potential mechanism behind sleep disturbances associated with the disease and the potential treatment strategies.
神经元蜡样脂褐质沉积症（NCLs）是一组隐性遗传的神经退行性疾病，其特征是溶酶体中储存有荧光物质。CLN3病，即青少年型巴滕病，是最常见的NCL，由神经元蜡样脂褐质沉积症3（CLN3）基因突变引起。睡眠障碍是与CLN3病相关的最常见症状之一，会降低患者的生活质量，但对此研究不足，且在该疾病的动物模型中尚未得到明确描述。当前的研究利用PiezoSleep，一种非侵入性的自动压电运动传感系统，对Cln3（Cln3KO）小鼠模型以及年龄和性别匹配的野生型（WT）对照小鼠的睡眠和清醒状态进行分类。在一小群野生型和Cln3KO小鼠中，当与包括脑电图（EEG）和肌电图（EMG）在内的同步多导睡眠图记录进行验证时，发现PiezoSleep对睡眠-清醒状态的分类准确率约为90%。我们的大样本PiezoSleep研究显示，与野生型雄性小鼠相比，雄性Cln3KO小鼠在光照期存在睡眠异常，与野生型雌性小鼠相比，Cln3KO雌性小鼠在黑暗期存在更细微的差异。我们对Cln3KO小鼠模型睡眠情况的描述与CLN3病患者出现的睡眠异常相符，并为继续研究CLN3病和其他NCLs常见的睡眠障碍奠定了基础。作为首个捕捉CLN3病睡眠障碍的动物模型研究，我们的工作将推动未来对该疾病相关睡眠障碍潜在机制及潜在治疗策略的研究。
