Parkinson-like early autonomic dysfunction induced by vagal application of DOPAL in rats.
Parkinson-like early autonomic dysfunction induced by vagal application of DOPAL in rats.
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DOI：
10.1111/cns.13589
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发表时间：
2021-05
影响因子：
5.5
通讯作者：
Li BY
中科院分区：
文献类型：
--
作者：
Sun J;He C;Yan QX;Wang HD;Li KX;Sun X;Feng Y;Zha RR;Cui CP;Xiong X;Gao S;Wang X;Yin RX;Qiao GF;Li BY
了解为什么自主神经衰竭（帕金森病 (PD) 的常见非运动症状）比典型的运动障碍发生得更早。迷走神经应用 DOPAL（3,4-二羟基苯乙醛）模拟 PD 样自主神经功能障碍，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间依赖性交替以及心脏和结节 (NG)/孤束核 (NTS) 的超微结构变化。 DOPAL 治疗大鼠的血压 (BP) 和压力反射敏感性显着降低，并伴随着立位血压的时间依赖性变化，这与超声心动图和心肌细胞线粒体超微结构的改变一致。值得注意的是，Mon-/Tri-α-突触核蛋白的时间依赖性和协同变化与 NG 和 NTS 的形态变化是平行的。这些都表明，迷走神经应用 DOPAL 介导的早期自主神经功能障碍高度表明 PD 的可能病因是从外周部位而不是中枢部位引发的。为PD的预防和早期诊断提供科学依据。 DOPAL 在迷走神经上的应用会导致 α-Syn 单体大量积累，形成有毒低聚物，这些低聚物可以通过轴突流转运到心脏 TA 和 NG-NTS
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. Application of DOPAL on Vagus causes significant accumulation of α‐Syn monomers to form toxic oligomers that could be transported to the heart TA and NG‐NTS by axon flow
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影响因子：
4.4
作者：
Kim, Joong-Seok;Park, Hyung-Eun;Lee, Kwang-Soo
通讯作者：
Lee, Kwang-Soo
影响因子：
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作者：
Follmer, Cristian;Coelho-Cerqueira, Eduardo;Eliezer, David
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帕金森病中有毒多巴胺代谢物 DOPAL 积累的决定因素。
影响因子：
4.7
作者：
Goldstein DS;Sullivan P;Holmes C;Miller GW;Alter S;Strong R;Mash DC;Kopin IJ;Sharabi Y
通讯作者：
Sharabi Y
DOI：
10.1124/jpet.118.248492
发表时间：
2018-07-01
影响因子：
3.5
作者：
Jinsmaa, Yunden;Sharabi, Yehonatan;Goldstein, David S.
通讯作者：
Goldstein, David S.
影响因子：
4.4
作者：
Klanbut, Siranan;Phattanarudee, Siripan;Bhidayasiri, Roongroj
通讯作者：
Bhidayasiri, Roongroj