The pedunculopontine tegmental nucleus is not important for breathing impairments observed in a Parkinson's disease model

Abstract

Parkinson's 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. Our main hypothesis is that degenerated PPTg neurons contribute to the blunted respiratory activity in a PD model. Adult mice (males and females) (CEUA: 6641200919) that express the fluorescent 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, 10 μg/μl). Ten days later, the animals were exposed to hypercapnia (7% CO2) or hypoxia (8% O2) to activate PPTg neurons. Vglut2-cre Ai6 animals also received retrograde tracer injections (cholera toxin b) into the retrotrapezoid nucleus (RTN) or preBötzinger Complex (preBötC) and anterograde tracer injections (AAV-mCherry) into the SNpc. In 6-OHDA-injected mice, there is 79% of reduction in the number of dopaminergic neurons in SNpc (95.09 ± 4.77 vs. vehicle: 456.6 ± 6 neurons) without changing the number of glutamatergic, GABAergic and cholinergic neurons in the PPTg. Hypercapnia activated fewer Vglut2 neurons in6-OHDA animals (8.6 ± 2.7 vs. vehicle 19.5 ± 2.9 neurons), and hypoxia did not activate PPTg neurons. PPTg neurons do not input RTN or preBötC 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 neurons activated by hypercapnia in the PD animal model, suggesting that PPTg may participate in the hypercapnia ventilatory response. Funding: FAPESP, CAPES and CNPq This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.