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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: Experimental Neurology; v. 302, p. 46-56, APR 2018.
• Web of Science Citations: 6

Abstract

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)

• FAPESP's process: 14/22406-1 - Respiratory anatomofunctional changes observed in an experimental model of Parkinson Disease
• Grantee: Ana Carolina Takakura Moreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/23281-3 - Encephalic regions responsible for neuroplasticity observed in respiratory response induced by hypercapnia in a modelo of Parkinson's Disease
• Grantee: Ana Carolina Takakura Moreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/18842-3 - Orexinergic and aminergic mechanisms in respiratory control in an animal model of Parkinsons Disease
• Grantee: Luiz Marcelo Oliveira Santos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/00103-4 - Anatomical projections between substantia nigra and retrotrapezoid nucleus
• Grantee: Marina Taranto Botelho
• Support Opportunities: Scholarships in Brazil - Scientific Initiation