The Pedunculopontine Tegmental Nucleus is not Important for Breathing Impairments Observed in a Parkinson?s Disease Model

Author(s)

Miranda, Nicole C. ; Oliveira, Luiz M. ; Aquino, Yasmin C. ; Moreira, Thiago S. ; Takakura, Ana C.

• Document type: Journal article
• Source: Neuroscience; v. 512, p. 15-pg., 2023-01-27.

Abstract

disease (PD) is a motor disorder resulting from degeneration of dopaminergic neurons of substantia nigra pars compacta (SNpc), with classical and non-classical symptoms such as respiratory instability. An important region for breathing control, the Pedunculopontine Tegmental Nucleus (PPTg), is composed of cholinergic, glutamatergic, and GABAergic neurons. We hypothesize that degenerated PPTg neurons in a PD model contribute to the blunted respiratory activity. Adult mice (40 males and 29 females) that express the fluo-rescent green protein in cholinergic, glutamatergic or GABAergic cells were used (Chat-cre Ai6, Vglut2-cre Ai6 and Vgat-cre Ai6) and received bilateral intrastriatal injections of vehicle or 6-hydroxydopamine (6-OHDA). Ten days later, the animals were exposed to hypercapnia or hypoxia to activate PPTg neurons. Vglut2-cre Ai6 animals also received retrograde tracer injections (cholera toxin b) into the retrotrapezoid nucleus (RTN) or preBotzinger Complex (preBotC) and anterograde tracer injections (AAV-mCherry) into the SNpc. In 6-OHDA-injected mice, there is a 77% reduction in the number of dopaminergic neurons in SNpc without changing the number of neurons in the PPTg. Hypercapnia activated fewer Vglut2 neurons in PD, and hypoxia did not activate PPTg neurons. PPTg neurons do not input RTN or preBotC regions but receive projections from SNpc. Although our results did not show a reduction in the number of glutamatergic neurons in PPTg, we observed a reduction in the number of neu-rons activated by hypercapnia in the PD animal model, suggesting that PPTg may participate in the hypercapnia ventilatory response.(c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 19/01236-4 - Effects of pharmacological and non-pharmacological treatments on respiratory changes observed in a murine model 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: 20/16320-8 - Investigation of the existence of anatomical projections from substantia nigra to pre-Bötzinger complex
• Grantee: Yasmin Cestari Aquino
• Support Opportunities: Scholarships in Brazil - Scientific Initiation