Department of Pharmacology, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, SP, 05508 Sao Paulo, SP, Brazil.
Department of Pharmacology, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, SP, 05508 Sao Paulo, SP, Brazil; Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA.
Exp Neurol. 2024 Oct;380:114924. doi: 10.1016/j.expneurol.2024.114924. Epub 2024 Aug 13.
Parkinson's disease (PD) involves the degeneration of dopaminergic neurons in the substantia nigra (SNpc) and manifests with both classic and non-classic motor symptoms, including respiratory failure. Our study aims to investigate the involvement of the commissural and intermediate nucleus of the solitary tract (cNTS and iNTS) in the attenuated respiratory response to hypoxia in PD. Using a PD rat model induced by bilateral injection of 6-hydroxydopamine (6-OHDA) into the striatum of male Wistar rats, we explored potential alterations in the population of Phox2b neurons or hypoxia-activated neurons in the NTS projecting to the retrotrapezoid nucleus (RTN). Additionally, we explored neuronal connectivity between SNpc and cNTS. Projections pathways were assessed using unilateral injection of the retrograde tracer Fluorogold (FG) in the cNTS and RTN. Neuronal activation was evaluated by analyzing fos expression in rats exposed to hypoxia. In the PD model, the ventilatory response, measured through whole-body plethysmography, was impaired at both baseline and in response to hypoxia. A reduction in Phox2b-expressing neurons or hypoxia-activated neurons projecting to the RTN was observed. Additionally, we identified an indirect pathway linking the SNpc and cNTS, which passes through the periaqueductal gray (PAG). In conclusion, our findings suggest impairment in the SNpc-PAG-cNTS pathway in the PD model, explaining the loss of Phox2b-expressing neurons or hypoxia-activated neurons in the cNTS and subsequent respiratory impairment during hypoxic stimulation. We propose that the reduced population of Phox2b-expressing neurons in the NTS may include the same neurons activated by hypoxia and projecting to the RTN.
帕金森病（PD）涉及黑质（SNpc）中多巴胺能神经元的退化，并表现出经典和非经典运动症状，包括呼吸衰竭。我们的研究旨在探讨连合核和中间孤束核（cNTS 和 iNTS）在 PD 患者对缺氧的呼吸反应减弱中的作用。使用 6-羟多巴胺（6-OHDA）双侧注射到雄性 Wistar 大鼠纹状体诱导的 PD 大鼠模型，我们探讨了投射到延髓梯形核（RTN）的 NTS 中 Phox2b 神经元或缺氧激活神经元的潜在变化。此外，我们还探讨了 SNpc 和 cNTS 之间的神经元连接。通过单侧注射逆行示踪剂 Fluorogold（FG）到 cNTS 和 RTN 来评估投射途径。通过分析暴露于缺氧环境下的大鼠中 fos 表达来评估神经元激活。在 PD 模型中，通过全身 plethysmography 测量的通气反应在基线和缺氧时都受损。观察到投射到 RTN 的 Phox2b 表达神经元或缺氧激活神经元减少。此外，我们确定了一条连接 SNpc 和 cNTS 的间接途径，该途径穿过导水管周围灰质（PAG）。总之，我们的研究结果表明，PD 模型中 SNpc-PAG-cNTS 途径受损，解释了 cNTS 中 Phox2b 表达神经元或缺氧激活神经元的丧失以及随后在缺氧刺激期间的呼吸受损。我们提出，NTS 中 Phox2b 表达神经元的减少可能包括对缺氧激活并投射到 RTN 的相同神经元。
