Respiratory disturbances present in Parkinson’s disease (PD) are not well understood. Thus, studies in animal models aimed to link brain dopamine (DA) deficits with respiratory impairment are needed. Adult Wistar rats were lesioned with injection of 6-hydroxydopamine (6-OHDA) into the third cerebral ventricle. Two weeks after hypoxic test was performed in whole-body plethysmography chamber, phrenic (PHR) and hypoglossal (HG) nerve activities were recorded in normoxic and hypoxic conditions in anesthetized, vagotomized, paralyzed and mechanically ventilated rats. The effects of activation and blockade of dopaminergic carotid body receptors were investigated during normoxia in anesthetized spontaneously breathing rats. 6-OHDA injection affected resting respiratory pattern in awake animals: an increase in tidal volume and a decrease in respiratory rate had no effect on minute ventilation. Hypoxia magnified the amplitude and minute activity of the PHR and HG nerve of 6-OHDA rats. The ratio of pre-inspiratory to inspiratory HG burst amplitude was reduced in normoxic breathing. Yet, the ratio of pre-inspiratory time to total time of the respiratory cycle was increased during normoxia. 6-OHDA lesion had no impact on DA and domperidone effects on the respiratory pattern, which indicate that peripheral DA receptors are not affected in this model. Analysis of monoamines confirmed substantial striatal depletion of dopamine, serotonin and noradrenaline (NA) and reduction of NA content in the brainstem. In bilateral 6-OHDA model changes in activity of both nerves: HG (linked with increased apnea episodes) and PHR are present. Demonstrated respiratory effects could be related to specific depletion of DA and NA.

中文翻译：

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6-OHDA 诱导的双侧帕金森病模型常氧和缺氧期间的呼吸模式以及膈神经和舌下神经活动


帕金森病 (PD) 中存在的呼吸障碍尚不清楚。因此，需要在动物模型中进行研究，旨在将大脑多巴胺（DA）缺陷与呼吸障碍联系起来。将 6-羟基多巴胺 (6-OHDA) 注射到第三脑室中，使成年 Wistar 大鼠受到损伤。在全身体积描记室中进行低氧测试两周后，记录麻醉、迷走神经切断、麻痹和机械通气大鼠在常氧和低氧条件下的膈（PHR）和舌下（HG）神经活动。研究了麻醉自主呼吸大鼠在常氧状态下激活和阻断多巴胺能颈动脉体受体的影响。 6-OHDA 注射影响清醒动物的静息呼吸模式：潮气量的增加和呼吸频率的降低对每分钟通气量没有影响。缺氧放大了6-OHDA大鼠PHR和HG神经的振幅和分钟活动。在含氧量正常的呼吸中，吸气前与吸气时 HG 爆发幅度的比率降低。然而，在常氧状态下，吸气前时间与呼吸周期总时间的比率增加。 6-OHDA损伤对DA和多潘立酮对呼吸模式的影响没有影响，这表明在该模型中外周DA受体不受影响。单胺分析证实，纹状体中多巴胺、血清素和去甲肾上腺素 (NA) 明显减少，脑干中 NA 含量减少。在双侧 6-OHDA 模型中，双侧神经活动发生变化：存在 HG（与呼吸暂停次数增加相关）和 PHR。已证实的呼吸效应可能与 DA 和 NA 的特定消耗有关。