Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China.
School of Pharmaceutical Science, Sun Yat-Sen University, Shenzhen, China.
CNS Neurosci Ther. 2021 May;27(5):540-551. doi: 10.1111/cns.13589. Epub 2021 Jan 21.
To understand why autonomic failures, a common non-motor symptom of Parkinson's disease (PD), occur earlier than typical motor disorders.
Vagal application of DOPAL (3,4-dihydroxyphenylacetaldehyde) to simulate PD-like autonomic dysfunction and understand the connection between PD and cardiovascular dysfunction. Molecular and morphological approaches were employed to test the time-dependent alternation of α-synuclein aggregation and the ultrastructure changes in the heart and nodose (NG)/nucleus tractus solitarius (NTS).
Blood pressure (BP) and baroreflex sensitivity of DOPAL-treated rats were significantly reduced accompanied with a time-dependent change in orthostatic BP, consistent with altered echocardiography and cardiomyocyte mitochondrial ultrastructure. Notably, time-dependent and collaborated changes in Mon-/Tri-α-synuclein were paralleled with morphological alternation in the NG and NTS.
These all demonstrate that early autonomic dysfunction mediated by vagal application of DOPAL highly suggests the plausible etiology of PD initiated from peripheral, rather than central site. It will provide a scientific basis for the prevention and early diagnosis of PD.
了解为什么自主功能衰竭，帕金森病（PD）的一种常见非运动症状，比典型的运动障碍出现得更早。
通过迷走神经应用 DOPAL（3,4-二羟基苯乙醛）来模拟 PD 样自主功能障碍，并了解 PD 与心血管功能障碍之间的联系。采用分子和形态学方法来测试α-突触核蛋白聚集的时变和心脏及结状神经节（NG）/孤束核（NTS）的超微结构变化。
DOPAL 处理大鼠的血压（BP）和压力反射敏感性显著降低，伴有体位性 BP 的时变改变，与改变的超声心动图和心肌细胞线粒体超微结构一致。值得注意的是，Mon-/Tri-α-突触核蛋白的时变和协作变化与 NG 和 NTS 的形态变化平行。
这些都表明，迷走神经应用 DOPAL 介导的早期自主功能障碍高度提示 PD 的发病机制可能起源于外周，而不是中枢部位。它将为 PD 的预防和早期诊断提供科学依据。
