Sleepiness in Parkinson's Disease

描述（由申请人提供）：据估计，高达50%的帕金森病（PD）患者患有白天过度嗜睡（EDS），这是一种慢性进行性神经退行性疾病，通常会损害运动技能（肌肉僵硬、震颤和运动迟缓）。此外，猝发睡眠发作（SA）（无前驱的睡眠发作）出现在PD中，这种症状更常发生在服用多巴胺D2/3激动剂的患者中。人们对PD患者的运动障碍给予了相当大的关注，而对不可抗拒的白天嗜睡却很少关注。虽然这些睡眠症状也显著影响患者的生活质量或威胁他们的健康

DESCRIPTION (provided by applicant): It is estimated that up to 50% of patients with Parkinson's disease (PD), a chronically progressive neurodegenerative disease that often impairs motor skills (muscle rigidity, tremor and bradykinesia), have suffered from excessive daytime sleepiness (EDS). In addition, sudden onsets of sleep attacks (SA) (sleep episodes without prodroma) appear in PD, with this symptom occurring more often in those patients who intake dopamine D2/3 agonists. Considerable attention has been devoted to the movement impairments in PD, while little attention has been paid to irresistible daytime sleepiness. Although these sleep symptoms also significantly affect patients' quality of life or threaten their lives (i.e., car accidents), current research does not focus on these symptoms, and the pathological mechanism involved in EDS/SA is unknown. Considering that dopaminergic transmission is impaired and D2/3 agonists trigger sleep symptoms in PD patients, combined with the fact that most wake- promoting compounds enhance dopaminergic neurotransmission, the D2/3 autoreceptor-mediated inhibitory dopaminergic neurotransmission likely plays a key role in EDS/SA in PD. In this proposal, we will dissect mechanisms responsible for EDS and dopamine agonist-induced SA in PD patients using the new genetic mouse model of PD (i.e., Mitopark mouse) by systematic evaluations of sleep behavior and monitoring of dopamine release before and after administration of D2/3 agonists in normal and Mitopark PD mice. The results of the study will determine the major factor(s) contributing to the D2/3 agonist induced pathological sleepiness in PD, and prove informative in preventing/treating this life-threatening, disabling disease. PUBLIC HEALTH RELEVANCE: It is estimated that up to 50% of patients with Parkinson's disease (PD) have suffered from excessive daytime sleepiness (EDS). In addition, sudden onsets of sleep attacks (SA), (which are sleep episodes without prodroma) occur in PD, and the PD patients who intake dopamine D2/3 agonists more often exhibit this disabling symptom. Systematic evaluations of sleep behavior and monitoring of dopamine release before and after administration of D2/3 agonists in a normal and a genetic mouse model of PD will be performed in order to evaluate if altered D2/D3 receptor sensitivity contributes to EDS/SA in PD.