Stimulation of retrotrapezoid nucleus Phox2b-expressing neurons rescues breathing dysfunction in an experimental Parkinson's disease rat model

Autor(es)

Fernandes-Junior, Silvio A. ^{[1, 2]} ; Oliveira, Luiz M. ^[1] ; Czeisler, Catherine M. ^[2] ; Mo, Xiaokui ^{[3, 4]} ; Roy, Sashwati ^[5] ; Somogyi, Arpad ^[6] ; Zhang, Liewn ^[6] ; Moreira, Thiago S. ^[7] ; Otero, Jose J. ^[2] ; Takakura, Ana C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Pharmacol, 1524 Prof Lineu Prestes Ave, BR-05508000 Sao Paulo, SP - Brazil

^[2] Ohio State Univ OSU, Sch Med, Dept Pathol, Columbus, OH - USA

^[3] Ohio State Univ OSU, Dept Biostat & Bioinformat, Columbus, OH - USA

^[4] Ohio State Univ OSU, Dept Surg, Columbus, OH - USA

^[5] Ohio State Univ OSU, Dept Mol & Cellular Biochem, Columbus, OH - USA

^[6] Ohio State Univ OSU, Mass Spectrometry & Prote Facil, Columbus, OH - USA

^[7] Univ Sao Paulo, Inst Ciencias Biomed, Dept Physiol & Biophys, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Brain Pathology; v. 30, n. 5 JUL 2020.
• Citações Web of Science: 0

Resumo

Emerging evidence from multiple studies indicates that Parkinson's disease (PD) patients suffer from a spectrum of autonomic and respiratory motor deficiencies in addition to the classical motor symptoms attributed to substantia nigra degeneration of dopaminergic neurons. Animal models of PD show a decrease in the resting respiratory rate as well as a decrease in the number ofPhox2b-expressing retrotrapezoid nucleus (RTN) neurons. The aim of this study was to determine the extent to which substantia nigra pars compact (SNc) degeneration induced RTN biomolecular changes and to identify the extent to which RTN pharmacological or optogenetic stimulations rescue respiratory function following PD-induction. SNc degeneration was achieved in adult male Wistar rats by bilateral striatal 6-hydroxydopamine injection. For proteomic analysis, laser capture microdissection and pressure catapulting were used to isolate the RTN for subsequent comparative proteomic analysis and Ingenuity Pathway Analysis (IPA). The respiratory parameters were evaluated by whole-body plethysmography and electromyographic analysis of respiratory muscles. The results confirmed reduction in the number of dopaminergic neurons of SNc and respiratory rate in the PD-animals. Our proteomic data suggested extensive RTN remodeling, and that pharmacological or optogenetic stimulations of the diseased RTN neurons promoted rescued the respiratory deficiency. Our data indicate that despite neuroanatomical and biomolecular RTN pathologies, that RTN-directed interventions can rescue respiratory control dysfunction. (AU)

• Processo FAPESP: 16/23281-3 - Regiões encefálicas responsáveis pela neuroplasticidade observada na resposta respiratória induzida por hipercapnia em modelo animal de Doença de Parkinson
• Beneficiário: Ana Carolina Takakura Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/20695-6 - Análise da ativação seletiva de neurônios bulbares em modelo experimental da Doença de Parkinson: um estudo temporal dos possíveis mecanismos para restauração da função respiratória
• Beneficiário: Silvio de Araujo Fernandes Junior
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/23376-1 - Núcleo retrotrapezóide, quimiossensibilidade central e automaticidade respiratória
• Beneficiário: Thiago dos Santos Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/11165-1 - O déficit respiratório em um modelo experimental da Doença de Parkinson pode estar associado a alterações no gene Phox2b ao nível da medula ventrolateral
• Beneficiário: Silvio de Araujo Fernandes Junior
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado