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Nucleus of the solitary tract neuronal degeneration and impaired hypoxia response in a model of Parkinson's disease.
Naccarato, Monique C; Oliveira, Luiz M; Ferreira, Caroline B; Moreira, Thiago S; Takakura, Ana C.
Afiliação
  • Naccarato MC; Department of Pharmacology, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, SP, 05508 Sao Paulo, SP, Brazil.
  • Oliveira LM; 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.
  • Ferreira CB; Department of Pharmacology, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, SP, 05508 Sao Paulo, SP, Brazil; Department of Neurobiology, University of Pittsburgh School of Medicine, USA.
  • Moreira TS; Department of Physiology and Biophysics, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, SP, 05508 Sao Paulo, SP, Brazil.
  • Takakura AC; Department of Pharmacology, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, SP, 05508 Sao Paulo, SP, Brazil. Electronic address: takakura@icb.usp.br.
Exp Neurol ; 380: 114924, 2024 Oct.
Article em En | MEDLINE | ID: mdl-39147260
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxidopamina / Ratos Wistar / Núcleo Solitário / Hipóxia Limite: Animals Idioma: En Revista: Exp Neurol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxidopamina / Ratos Wistar / Núcleo Solitário / Hipóxia Limite: Animals Idioma: En Revista: Exp Neurol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos