Division of Neurobiology, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Division of Neuropathology, UCL Queen Square Institute of Neurology, University College London, London, UK.
Mov Disord. 2020 Dec;35(12):2333-2338. doi: 10.1002/mds.28229. Epub 2020 Sep 3.
Multiple system atrophy (MSA) and Parkinson's disease (PD) patients develop respiratory and cardiovascular disturbances including obstructive sleep apnea, orthostatic hypotension, and nocturnal stridor. We hypothesized that, associated with these respiratory and cardiovascular disturbances, hypoxic events may occur in MSA and PD brains that may play a role in disease progression. The objective of this study was to evaluate the presence of hypoxia in nonneurological controls and PD and MSA patients.
Molecular levels of hypoxia markers were measured in postmortem brain tissue from controls and PD and MSA cases.
MSA brain showed signs of chronic hypoxia characterized by the significant accumulation of the hypoxic marker HIF2α as compared to PD patients and controls. We detected no differences between MSA subtypes. Signs of hypoxia were also observed in PD patients with a clinical presentation similar to the MSA cases.
The results obtained from this study suggest a new alternative pathway associated with α-synucleinopathies that may contribute to the pathogenesis of these disorders. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
多系统萎缩（MSA）和帕金森病（PD）患者会出现呼吸和心血管紊乱，包括阻塞性睡眠呼吸暂停、体位性低血压和夜间喘鸣。我们假设，与这些呼吸和心血管紊乱相关，MSA 和 PD 大脑中可能会发生缺氧事件，这可能在疾病进展中起作用。本研究的目的是评估非神经科对照组以及 PD 和 MSA 患者中缺氧的存在情况。
在对照组和 PD 及 MSA 病例的死后脑组织中测量缺氧标志物的分子水平。
与 PD 患者和对照组相比，MSA 大脑表现出慢性缺氧的迹象，其特征是缺氧标志物 HIF2α 的显著积累。我们在 MSA 亚型之间未发现差异。在临床表现类似于 MSA 病例的 PD 患者中也观察到了缺氧的迹象。
本研究的结果表明，与α-突触核蛋白病相关的一种新的替代途径可能有助于这些疾病的发病机制。
