Andrzejewski Kryspin, Orłowska Magdalena E, Zaremba Małgorzata, Joniec-Maciejak Ilona, Kaczyńska Katarzyna
Department of Respiration Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego 5 St., 02-106, Warsaw, Poland.
Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research (CePT), Medical University of Warsaw, 02-091, Warsaw, Poland.
Sci Rep. 2025 Jul 16;15(1):25712. doi: 10.1038/s41598-025-10994-z.
The main symptoms of Parkinson's disease (PD) affect physical movement, but are often associated with a wide range of non-motor symptoms, as well as breathing disorders. Of these, respiratory muscle weakness, decreased air passage resulting in restrictive breathing changes, respiratory rhythm abnormalities, and upper airway dysfunction are usually indicated. To study respiratory impairment in PD, we used a rat model of PD induced by bilateral injection of 6-hydroxydopamine (6-OHDA) into the striatum. We investigated the ventilatory response to hypercapnia (HCVR) and the phenomenon of phrenic long-term depression (pLTD). To determine the effect of serotonergic system activation on HCVR we used fluoxetine, a selective serotonin reuptake inhibitor (SSRI), and 5-hydroxy-L-tryptophan (5-HTP), a precursor of serotonin (5-HT) synthesis. Treatment with both serotonergic agents did not affect air breathing in 6-OHDA and sham rats, while the impaired HCVR in the PD model was restored to the values present in the control group. Moreover, we also showed that pLTD was fully expressed only in sham rats. The 6-OHDA rats showed significantly reduced pLTD, indicating a disruption in the brainstem structures that regulate this phenomenon. The changes in respiration were accompanied by a significant reduction in striatal dopamine levels and a smaller but significant reduction in serotonin concentration in the striatum and brainstem shown by HPLC analysis. Our results indicate a possible degeneration of the serotonergic system in this model, which may have influenced the impairment of HCVR and pLTD. Activation of the serotonergic system eliminating blunted HCVR indicates its potential in alleviating respiratory distress.
帕金森病（PD）的主要症状影响身体运动，但通常与多种非运动症状以及呼吸障碍有关。其中，通常表现为呼吸肌无力、气道变窄导致限制性呼吸变化、呼吸节律异常和上气道功能障碍。为了研究帕金森病中的呼吸功能损害，我们使用了一种通过双侧向纹状体注射6-羟基多巴胺（6-OHDA）诱导的帕金森病大鼠模型。我们研究了对高碳酸血症的通气反应（HCVR）和膈神经长期抑制（pLTD）现象。为了确定血清素能系统激活对HCVR的影响，我们使用了氟西汀（一种选择性5-羟色胺再摄取抑制剂（SSRI））和5-羟基-L-色氨酸（5-HTP，血清素（5-HT）合成的前体）。两种血清素能药物治疗均未影响6-OHDA大鼠和假手术大鼠的空气呼吸，而帕金森病模型中受损的HCVR恢复到了对照组的水平。此外，我们还表明，pLTD仅在假手术大鼠中完全表达。6-OHDA大鼠的pLTD显著降低，表明调节该现象的脑干结构受到破坏。呼吸变化伴随着纹状体多巴胺水平的显著降低，以及通过高效液相色谱分析显示的纹状体和脑干中血清素浓度较小但显著的降低。我们的结果表明，该模型中血清素能系统可能发生退化，这可能影响了HCVR和pLTD的损害。血清素能系统的激活消除了钝化的HCVR，表明其在缓解呼吸窘迫方面的潜力。
