Pink1 -/- Rats Show Early-Onset Swallowing Deficits and Correlative Brainstem Pathology.
Pink1 -/- Rats Show Early-Onset Swallowing Deficits and Correlative Brainstem Pathology.
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DOI：
10.1007/s00455-018-9896-5
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发表时间：
2018-12
期刊：
影响因子：
2.6
通讯作者：
Ciucci MR
中科院分区：
文献类型：
--
作者：
Cullen KP;Grant LM;Kelm-Nelson CA;Brauer AFL;Bickelhaupt LB;Russell JA;Ciucci MR
帕金森病 (PD) 会影响口咽吞咽功能，从而对生活质量产生负面影响并导致吸入性肺炎。吞咽困难通常在疾病过程的早期就开始出现，并且通过标准治疗无法改善。因此，PD 人群的吞咽障碍得不到充分治疗。 Pink1 −/− 大鼠用于建立帕金森病模型，并展示了广泛的脑干神经病理学与早发性感觉运动功能障碍的结合；然而，迄今为止，吞咽行为尚未得到评估。为了检验 Pink1 −/− 大鼠在吞咽方面表现出早发型差异的假设，我们使用视频荧光镜检查分析了受试者内的口咽吞咽情况。对 4 个月（Pink1 −/− n = 16，WT = 16）和 8 个月（Pink1 −/− n = 12，WT = 12）的 Pink1 −/− 和野生型 (WT) 对照进行了测试。 Pink1 −/− 大鼠在 4 个月和 8 个月时的平均和最大推注量均显着增加。所有动物的推注平均速度在 8 个月时有所增加；然而，与 WT 相比，Pink1 −/− 动物在 8 个月时的速度显着增加。数据显示，8 个月时 Pink1 −/− 大鼠的咀嚼率显着降低，表明口部运动功能障碍在这个时间点开始出现。确定了吞咽变量与神经病理学结果之间的关系，例如 Pink1 −/− 大鼠中疑核中的 α-突触核蛋白增加和蓝斑中去甲肾上腺素能细胞的减少。 Pink1−/− PD 大鼠模型中早期口咽吞咽缺陷的存在及其与脑干病理学的关系表明，这可能是早期吞咽缺陷及其机制的有用模型。这些发现提示了帕金森吞咽困难的早期检测和治疗的临床意义。
Parkinson disease (PD) compromises oropharyngeal swallowing, which negatively affects quality of life and contributes to aspiration pneumonia. Dysphagia often begins early in the disease process, and does not improve with standard therapies. As a result, swallowing deficits are undertreated in the PD population. The Pink1 −/− rat is used to model PD, and demonstrates widespread brainstem neuropathology in combination with early-onset sensorimotor dysfunction; however, to date, swallowing behaviors have not been evaluated. To test the hypothesis that Pink1 −/− rats demonstrate early-onset differences in swallowing, we analyzed within-subject oropharyngeal swallowing using videofluoroscopy. Pink1 −/− and wildtype (WT) controls at 4 (Pink1 −/− n = 16, WT = 16) and 8 (Pink1 −/− n = 12, WT = 12) months of age were tested. The average and maximum bolus size was significantly increased in Pink1 −/− rats at both 4 and 8 months. Bolus average velocity was increased at 8 months for all animals; yet, Pink1 −/− animals had significantly increased velocities compared to WT at 8 months. The data show a significant reduction in mastication rate for Pink1 −/− rats at 8 months suggesting the onset of oromotor dysfunction begins at this time point. Relationships among swallowing variables and neuropathological findings, such as increased alpha-synuclein protein in the nucleus ambiguus and reductions in noradrenergic cells in the locus coeruleus in the Pink1 −/− rats, were determined. The presence of early oropharyngeal swallowing deficits and relationships to brainstem pathology in Pink1−/− rat models of PD indicate that this may be a useful model of early swallowing deficits and their mechanisms. These findings suggest clinical implications for early detection and management of dysphagia in PD.
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