The involvement of the pathway connecting the substantia nigra, the periaqueductal gray matter and the retrotrapezoid nucleus in breathing control in a rat model of Parkinson's disease

Autor(es)

Lima, Juliana C. ^[1] ; Oliveira, Luiz M. ^[1] ; Botelho, Marina T. ^[1] ; Moreira, Thiago S. ^[2] ; Takakura, Ana C. ^[1]

Afiliação do(s) autor(es)

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

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Neurology; v. 302, p. 46-56, APR 2018.
• Citações Web of Science: 6

Resumo

Parkinson's disease (PD) is characterized by a reduction in the number of dopaminergic neurons of the substantia nigra (SNpc), accompanied by motor and non-motor deficiencies such as respiratory failure. Here, our aim was to investigate possible neuronal communications between the SNpc and chemoreceptor neurons within the retrotrapezoid nucleus (RTN), in order to explain neurodegeneration and the loss of breathing function in the 6OHDA PD animal model. Male Wistar rats received tracer injections in the SNpc, RTN and periaqueductal gray (PAG) regions to investigate the projections between those regions. The results showed that neurons of the SNpc project to the RTN by an indirect pathway that goes through the PAG region. In different groups of rats, reductions in the density of neuronal markers (NeuN) and the number of catecholaminergic varicosities in PAG, as well as reductions in the number of CO2-activated PAG neurons with RTN projections, were observed in a 6OHDA model of PD. Physiological experiments showed that inhibition of the PAG by bilateral injection of muscimol did not produce resting breathing disturbances but instead reduced genioglossus (GG(EMG)) and abdominal (Abd(EMG)) muscle activity amplitude induced by hypercapnia in control rats that were urethane-anesthetized, vagotomized, and artificially ventilated. However, in a model of PD, we found reductions in resting diaphragm muscle activity (Dia(EMG)) and GG(EMG) frequencies, as well as in hypercapnia-induced Dia(EMG), GG(EMG) and Abd(EMG) frequencies and GG(EMG) and Abd(EMG) amplitudes. Therefore, we can conclude that there is an indirect pathway between neurons of the SNpc and RTN that goes through the PAG and that there is a defect of this pathway in an animal model of PD. (AU)

• Processo FAPESP: 14/22406-1 - Alterações respiratórias anatomofuncionais observadas em um modelo experimental da Doença de Parkinson
• Beneficiário: Ana Carolina Takakura Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• 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: 15/23376-1 - Núcleo retrotrapezóide, quimiossensibilidade central e automaticidade respiratória
• Beneficiário: Thiago dos Santos Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/18842-3 - Mecanismos orexinérgicos e aminérgicos no controle respiratório em modelo animal de Doença de Parkinson
• Beneficiário: Luiz Marcelo Oliveira Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/00103-4 - Projeções anatômicas existentes entre a substância negra e o núcleo retrotrapezóide
• Beneficiário: Marina Taranto Botelho
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica