Neurology Department, Escola Paulista de Medicina Universidade Federal de São Paulo, São Paulo, Brazil.
Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cádiz, Cádiz, Spain.
Exp Physiol. 2022 Nov;107(11):1349-1359. doi: 10.1113/EP090378. Epub 2022 Sep 8.
What is the central question of this study? How does the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease model affect the respiratory response in female rats? What effect does ovariectomy have on that response? What is the main finding and its importance? The results suggest a protective effect of ovarian hormones in maintaining normal neuroanatomical integrity of the medullary respiratory nucleus in females. It was observed that ovariectomy alone reduced neurokinin-1 density in the pre-Bötzinger complex and Bötzinger complex, and there was an incremental effect of 6-OHDA and ovariectomy on retrotrapezoid nucleus neurons.
Emerging evidence indicates that the course of Parkinson's disease (PD) includes autonomic and respiratory deficiencies in addition to the classical motor symptoms. The prevalence of PD is lower in women, and it has been hypothesized that neuroprotection by ovarian hormones can explain this difference. While male PD animal models present changes in the central respiratory control areas, as well as ventilatory parameters under normoxia and hypercapnia, little is known about sex differences regarding respiratory deficits in this disease background. This study aimed to explore the neuroanatomical and functional respiratory changes in intact and ovariectomized (OVX) female rats subjected to chemically induced PD via a bilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA). The respiratory parameters were evaluated by whole-body plethysmography, and the neuroanatomy was monitored using immunohistochemistry. It was found that dopaminergic neurons in the substantia nigra and neurokinin-1 receptor density in the rostral ventrolateral respiratory group, Bötzinger and pre-Bötzinger complex were reduced in the chemically induced PD animals. Additionally, reduced numbers of Phox2b neurons were only observed in the retrotrapezoid nucleus of PD-OVX rats. Concerning respiratory parameters, in OVX rats, the resting and hypercapnia-induced tidal volume (V ) is reduced, and ventilation ( ) changes independently of 6-OHDA administration. Notably, there is a reduction in the number of retrotrapezoid nucleus Phox2b neurons and hypercapnia-induced respiratory changes in PD-OVX animals due to a 6-OHDA and OVX interaction. These results suggest a protective effect induced by ovarian hormones in neuroanatomical changes observed in a female experimental PD model.
本研究的核心问题是什么？6-羟多巴胺（6-OHDA）诱导的帕金森病模型如何影响雌性大鼠的呼吸反应？卵巢切除术对此反应有何影响？主要发现及其重要性是什么？结果表明，卵巢激素在维持雌性延髓呼吸核神经解剖完整性方面具有保护作用。研究观察到，单独卵巢切除术降低了 Pre-Bötzinger 复合体和 Bötzinger 复合体中的神经激肽-1 密度，6-OHDA 和卵巢切除术对梯形核神经元有累加效应。
越来越多的证据表明，帕金森病（PD）的病程包括自主神经和呼吸功能缺陷，除了经典的运动症状。女性 PD 的患病率较低，有人假设卵巢激素的神经保护作用可以解释这种差异。虽然雄性 PD 动物模型在中枢呼吸控制区以及常氧和高碳酸血症下的通气参数方面发生变化，但对于这种疾病背景下的呼吸缺陷，关于性别差异的研究甚少。本研究旨在探讨完整和卵巢切除（OVX）雌性大鼠在双侧纹状体注射 6-羟多巴胺（6-OHDA）诱导的化学性 PD 后神经解剖和功能呼吸变化。通过全身 plethysmography 评估呼吸参数，并用免疫组织化学监测神经解剖结构。结果发现，黑质多巴胺能神经元和头侧腹外侧呼吸组、Bötzinger 和 Pre-Bötzinger 复合体中的神经激肽-1 受体密度在化学诱导的 PD 动物中减少。此外，只有 PD-OVX 大鼠的梯形核中才观察到 Phox2b 神经元数量减少。关于呼吸参数，在 OVX 大鼠中，静息和高碳酸血症诱导的潮气量（V）减少，通气（）变化独立于 6-OHDA 给药。值得注意的是，由于 6-OHDA 和 OVX 的相互作用，PD-OVX 动物的梯形核 Phox2b 神经元数量减少和高碳酸血症诱导的呼吸变化。这些结果表明，卵巢激素在雌性实验性 PD 模型中观察到的神经解剖变化中具有保护作用。
