RESUMO
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.
Assuntos
Hipóxia , Oxidopamina , Ratos Wistar , Núcleo Solitário , Animais , Masculino , Ratos , Núcleo Solitário/patologia , Hipóxia/patologia , Oxidopamina/toxicidade , Proteínas de Homeodomínio/metabolismo , Modelos Animais de Doenças , Degeneração Neural/patologia , Neurônios/patologia , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/fisiopatologia , Fatores de Transcrição/metabolismoRESUMO
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, mainly affecting people over 60 yr of age. Patients develop both classic symptoms (tremors, muscle rigidity, bradykinesia, and postural instability) and nonclassical symptoms (orthostatic hypotension, neuropsychiatric deficiency, sleep disturbances, and respiratory disorders). Thus, patients with PD can have a significantly impaired quality of life, especially when they do not have multimodality therapeutic follow-up. The respiratory alterations associated with this syndrome are the main cause of mortality in PD. They can be classified as peripheral when caused by disorders of the upper airways or muscles involved in breathing and as central when triggered by functional deficits of important neurons located in the brainstem involved in respiratory control. Currently, there is little research describing these disorders, and therefore, there is no well-established knowledge about the subject, making the treatment of patients with respiratory symptoms difficult. In this review, the history of the pathology and data about the respiratory changes in PD obtained thus far will be addressed.