Sleep alterations in an environmental neurotoxin-induced model of parkinsonism.
Sleep alterations in an environmental neurotoxin-induced model of parkinsonism.
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DOI：
10.1016/j.expneurol.2010.08.005
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发表时间：
2010-11
影响因子：
5.3
通讯作者：
Mong JA
中科院分区：
文献类型：
--
作者：
McDowell KA;Hadjimarkou MM;Viechweg S;Rose AE;Clark SM;Yarowsky PJ;Mong JA
帕金森病（PD）的经典定义是由于基底神经节回路中多巴胺产生减少而导致的运动障碍。为了在严重运动功能障碍发生之前更好地诊断和治疗帕金森病，最近的注意力集中在早期非运动症状上，其中包括但不限于睡眠障碍，如日间过度嗜睡 (EDS) 和快速眼动行为障碍 (RBD)。然而，很少有动物模型能够复制帕金森病的运动和非运动症状。在这里，我们提出了一种进行性帕金森病大鼠模型，该模型显示出睡眠/觉醒模式的紊乱。流行病学研究阐明了关岛肌萎缩性脊髓侧索硬化症/帕金森病痴呆综合症 (ALS/PDC) 的变体与食用密克罗尼西亚苏铁植物 (苏铁) 洗过的种子制成的面粉之间的联系。我们的研究考察了长期食用苏铁对雄性斯普拉格-道利大鼠睡眠/觉醒活动的影响。与对照大鼠相比，苏铁喂养的大鼠表现出快速眼动 (REM) 睡眠和非快速眼动 (NREM) 睡眠的长度和/或次数增加，但以活动期间的清醒为代价。这种嗜睡行为表明无法维持觉醒。此外，喂食苏铁的大鼠下丘脑中的食欲素细胞显着减少。我们的结果揭示了一种新的帕金森病啮齿动物模型，其中包括可能与食欲素神经元失调有关的 EDS 样综合征。这种早期非运动症状的进一步表征可能为帕金森病的治疗提供潜在的治疗干预措施。
Parkinson’s disease (PD) is classically defined as a motor disorder resulting from decreased dopamine production in the basal ganglia circuit. In an attempt to better diagnose and treat PD before the onset of severe motor dysfunction, recent attention has focused on the early, non-motor symptoms, which include but are not limited to sleep disorders such as excessive daytime sleepiness (EDS) and REM behavioral disorder (RBD). However, few animal models have been able to replicate both the motor and non-motor symptoms of PD. Here, we present a progressive rat model of parkinsonism that displays disturbances in sleep/wake patterns. Epidemiological studies elucidated a link between the Guamanian variant of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) and the consumption of flour made from the washed seeds of the plant Cycas micronesica (cycad). Our study examined the effects of prolonged cycad consumption on sleep/wake activity in male, Sprague–Dawley rats. Cycad-fed rats exhibited an increase in length and/or number of bouts of rapid eye movement (REM) sleep and Non-REM (NREM) sleep at the expense of wakefulness during the active period when compared to control rats. This hypersomnolent behavior suggests an inability to maintain arousal. In addition, cycad-fed rats had significantly fewer orexin cells in the hypothalamus. Our results reveal a novel rodent model of parkinsonism that includes an EDS-like syndrome that may be associated with a dysregulation of orexin neurons. Further characterization of this early, non-motor symptom, may provide potential therapeutic interventions in the treatment of PD.
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影响因子：
3.3
作者：
Gerashchenko, D;Blanco-Centurion, C;Shiromani, PJ
通讯作者：
Shiromani, PJ
影响因子：
14.5
作者：
Fronczek, Rolf;Overeem, Sebastiaan;Swaab, Dick F.
通讯作者：
Swaab, Dick F.
影响因子：
5.3
作者：
Rao, Shyam D.;Banack, Sandra Anne;Weiss, John H.
通讯作者：
Weiss, John H.
影响因子：
5.6
作者：
Yi, Pei-Lu;Tsai, Chon-Haw;Chang, Fang-Chia
通讯作者：
Chang, Fang-Chia
影响因子：
11.2
作者：
LANGSTON, JW;FORNO, LS
通讯作者：
FORNO, LS