PDF(Pubmed)
Abstract：
In Parkinson\'s disease (PD), along with typical motor dysfunction, abnormal breathing is present; the cause of which is not well understood. The study aimed to analyze the effects of stimulation of the serotonergic system with 5-HT1A and 5-HT2A agonists in a model of PD induced by injection of 6-hydroxydopamine (6-OHDA). To model PD, bilateral injection of 6-OHDA into both striata was performed in male Wistar rats. Respiratory disturbances in response to 7% hypercapnia (CO2 in O2) in the plethysmographic chamber before and after stimulation of the serotonergic system and the incidence of apnea were studied in awake rats 5 weeks after 6-OHDA or vehicle injection. Administration of 6-OHDA reduced the concentration of serotonin (5-HT), dopamine (DA) and norepinephrine (NA) in the striatum and the level of 5-HT in the brainstem of treated rats, which have been associated with decreased basal ventilation, impaired respiratory response to 7% CO2 and increased incidence of apnea compared to Sham-operated rats. Intraperitoneal (i.p.) injection of the 5-HT1AR agonist 8-OH-DPAT and 5-HT2AR agonist NBOH-2C-CN increased breathing during normocapnia and hypercapnia in both groups of rats. However, it restored reactivity to hypercapnia in 6-OHDA group to the level present in Sham rats. Another 5-HT2AR agonist TCB-2 was only effective in increasing normocapnic ventilation in 6-OHDA rats. Both the serotonergic agonists 8-OH-DPAT and NBOH-2C-CN had stronger stimulatory effects on respiration in PD rats, compensating for deficits in basal ventilation and hypercapnic respiration. We conclude that serotonergic stimulation may have a positive effect on respiratory impairments that occur in PD.
摘要：
在帕金森病（PD）中，伴随着典型的运动功能障碍，存在异常呼吸；其原因尚不清楚。该研究旨在分析5-HT1A和5-HT2A激动剂在注射6-羟基多巴胺（6-OHDA）诱导的PD模型中刺激5-羟色胺能系统的作用。为PD建模，在雄性Wistar大鼠的两个纹状体双侧注射6-OHDA。在6-OHDA或赋形剂注射后5周，在清醒大鼠中研究了在刺激5-羟色胺能系统之前和之后对体积描记术室中7％高碳酸血症（O2中的CO2）的呼吸紊乱以及呼吸暂停的发生率。服用6-OHDA降低了5-羟色胺（5-HT）的浓度，治疗大鼠纹状体中的多巴胺（DA）和去甲肾上腺素（NA）以及脑干中的5-HT水平，这与基础通气减少有关，与假手术大鼠相比，对7％CO2的呼吸反应受损，呼吸暂停发生率增加。腹膜内（i.p.）注射5-HT1AR激动剂8-OH-DPAT和5-HT2AR激动剂NBOH-2C-CN可增加两组大鼠正常碳酸血症和高碳酸血症期间的呼吸。然而,它将6-OHDA组的高碳酸血症反应性恢复到Sham大鼠的水平。另一种5-HT2AR激动剂TCB-2仅在增加6-OHDA大鼠的正常通气方面有效。5-羟色胺能激动剂8-OH-DPAT和NBOH-2C-CN对PD大鼠的呼吸有较强的刺激作用,补偿基础通气和高碳酸血症呼吸的不足。我们得出的结论是，5-羟色胺能刺激可能对PD中发生的呼吸障碍产生积极影响。
