Emerging evidence from multiple studies indicates that Parkinson’s disease (PD) patients suffer from a spectrum of autonomic and respiratory motor deficiencies in addition to the classical motor symptoms attributed to substantia nigra degeneration of dopaminergic neurons. Animal models of PD show a decrease in the resting respiratory rate as well as a decrease in the number of Phox2b‐expressing retrotrapezoid nucleus (RTN) neurons. The aim of this study was to determine the extent to which substantia nigra pars compact (SNc) degeneration induced RTN biomolecular changes and to identify the extent to which RTN pharmacological or optogenetic stimulations rescue respiratory function following PD‐induction. SNc degeneration was achieved in adult male Wistar rats by bilateral striatal 6‐hydroxydopamine injection. For proteomic analysis, laser capture microdissection and pressure catapulting were used to isolate the RTN for subsequent comparative proteomic analysis and Ingenuity Pathway Analysis (IPA). The respiratory parameters were evaluated by whole‐body plethysmography and electromyographic analysis of respiratory muscles. The results confirmed reduction in the number of dopaminergic neurons of SNc and respiratory rate in the PD‐animals. Our proteomic data suggested extensive RTN remodeling, and that pharmacological or optogenetic stimulations of the diseased RTN neurons promoted rescued the respiratory deficiency. Our data indicate that despite neuroanatomical and biomolecular RTN pathologies, that RTN‐directed interventions can rescue respiratory control dysfunction.

中文翻译：

---

刺激后梯形核 Phox2b 表达神经元可挽救实验性帕金森病大鼠模型中的呼吸功能障碍。

多项研究的新证据表明，帕金森病 (PD) 患者除了具有多巴胺能神经元黑质变性引起的经典运动症状外，还患有一系列自主神经和呼吸运动缺陷。PD 动物模型显示静息呼吸频率降低以及Phox2b数量减少-表达逆梯形核（RTN）神经元。本研究的目的是确定黑质致密部 (SNc) 变性诱导 RTN 生物分子变化的程度，并确定 RTN 药理学或光遗传学刺激在 PD 诱导后挽救呼吸功能的程度。通过双侧纹状体 6-羟基多巴胺注射在成年雄性 Wistar 大鼠中实现了 SNc 变性。对于蛋白质组学分析，使用激光捕获显微切割和压力弹射分离 RTN，用于随后的比较蛋白质组学分析和独创性途径分析 (IPA)。通过全身体积描记法和呼吸肌肌电图分析评估呼吸参数。结果证实 PD 动物 SNc 的多巴胺能神经元数量和呼吸频率减少。我们的蛋白质组学数据表明广泛的 RTN 重塑，并且对患病的 RTN 神经元的药理学或光遗传学刺激促进了呼吸缺陷的挽救。我们的数据表明，尽管存在神经解剖学和生物分子 RTN 病理，但 RTN 导向的干预措施可以挽救呼吸控制功能障碍。