Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
Exp Neurol. 2017 Jul;293:172-180. doi: 10.1016/j.expneurol.2017.04.006. Epub 2017 Apr 19.
A previous study has demonstrated that in the 6-hydroxydopamine (6-OHDA)-model of Parkinson's disease (PD) there is a reduction in the number of Phox2b neurons in the retrotrapezoid nucleus (RTN) and a decrease in the respiratory response to hypercapnia 40days after PD-induction. The functional deficiency is restored 60days after 6-OHDA injection and here we tested the hypothesis that the locus coeruleus (LC) could be a candidate to restore the breathing deficiency. Minute Ventilation (V) in response to hypercapnia (7% CO) was assessed one day before, and then 40 and 60days after bilateral 6-OHDA (24μg/μL) or vehicle injections into the LC in control or PD-induced male Wistar rats. Bilateral injections of 6-OHDA decreased catecholaminergic neurons by 86% and 83% in the substantia nigra pars compacta (SNpc) and LC, respectively. As already described, in animals with lesions to the SNpc (N=6/group), the reduction in the ventilatory response to hypercapnia was restored 60days after PD (1257±81 vs. vehicle: 1185±49mL/kg/min). However, in animals with PD and lesion in the LC, the ventilation was blunted (674±39mL/kg/min). In another group of PD rats, we observed a reduction in the number of hypercapnia-induced-fos cells in the RTN region (40days: 38±3 and 60days: 8.5±0.9 vs. vehicle 78±3 cells) and an increase in the LC (40days: 46±4 and 60days: 94±22 vs. vehicle 1±1 cells). Our data suggest that LC catecholaminergic neurons can be a candidate structure mediating chemoreceptor function in a model of PD.
先前的研究表明，在帕金森病（PD）的 6-羟多巴胺（6-OHDA）模型中，Retrotrapezoid 核（RTN）中的 Phox2b 神经元数量减少，并且对高碳酸血症的呼吸反应在 PD 诱导后 40 天降低。功能缺陷在 6-OHDA 注射后 60 天恢复，在这里我们测试了蓝斑核（LC）可能是恢复呼吸缺陷的候选结构的假设。在双侧 6-OHDA（24μg/μL）或载体注射到对照组或 PD 诱导的雄性 Wistar 大鼠的 LC 之前一天、40 天和 60 天评估了对高碳酸血症（7%CO）的分钟通气量（V）。双侧 6-OHDA 注射分别使黑质致密部（SNpc）和 LC 中的儿茶酚胺能神经元减少 86%和 83%。正如已经描述的，在 SNpc 损伤的动物中（每组 6 只），对高碳酸血症的呼吸反应减少在 PD 后 60 天恢复（1257±81 与载体：1185±49mL/kg/min）。然而，在 LC 损伤的 PD 动物中，通气功能减弱（674±39mL/kg/min）。在另一组 PD 大鼠中，我们观察到 RTN 区域中高碳酸血症诱导的 fos 细胞数量减少（40 天：38±3 和 60 天：8.5±0.9 与载体 78±3 个细胞）和 LC 增加（40 天：46±4 和 60 天：94±22 与载体 1±1 个细胞）。我们的数据表明，LC 儿茶酚胺能神经元可能是 PD 模型中化学感受器功能的候选调节结构。
