Miranda Nicole C, Oliveira Luiz M, Moreira Thiago S, Ramirez Jan-Marino, Kalume Franck, Takakura Ana C
Department of Pharmacology, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, SP, São Paulo 05508-000, SP, Brazil.
Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA.
iScience. 2024 Oct 24;27(11):111251. doi: 10.1016/j.isci.2024.111251. eCollection 2024 Nov 15.
Parkinson's disease (PD) is a chronic neurodegenerative disorder affecting the motor system, with non-classic symptoms such as sleep disturbances and respiratory dysfunctions. These issues reflect a complex pathophysiological interaction that severely impacts quality of life. Using a 6-hydroxydopamine (6-OHDA) mouse model of PD, we investigated these connections by analyzing sleep patterns and respiratory parameters during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Our findings revealed altered breathing, including reduced respiratory frequency and increased apneas during both NREM and REM. To address these abnormalities, we employed chemogenetic stimulation of cholinergic neurons in the laterodorsal tegmental nucleus (LDTg), a key region for sleep-wake regulation and respiratory modulation. This intervention normalized respiratory function. These results highlight the critical role of LDTg cholinergic neurons in the coordinating sleep and breathing, suggesting that targeting these neurons could offer a therapeutic strategy for managing PD-related respiratory complications.
帕金森病（PD）是一种影响运动系统的慢性神经退行性疾病，伴有睡眠障碍和呼吸功能障碍等非典型症状。这些问题反映了一种复杂的病理生理相互作用，严重影响生活质量。我们使用帕金森病的6-羟基多巴胺（6-OHDA）小鼠模型，通过分析非快速眼动（NREM）和快速眼动（REM）睡眠期间的睡眠模式和呼吸参数来研究这些联系。我们的研究结果显示呼吸发生改变，包括在NREM和REM睡眠期间呼吸频率降低和呼吸暂停增加。为了解决这些异常情况，我们对脑桥背外侧被盖核（LDTg）中的胆碱能神经元进行了化学遗传学刺激，LDTg是睡眠-觉醒调节和呼吸调节的关键区域。这种干预使呼吸功能恢复正常。这些结果突出了LDTg胆碱能神经元在协调睡眠和呼吸方面的关键作用，表明针对这些神经元可能为管理帕金森病相关的呼吸并发症提供一种治疗策略。
