Sleep-related respiratory disruptions and laterodorsal tegmental nucleus in a mouse model of Parkinson’s disease
Nicole C. Miranda,
Luiz M. Oliveira,
Thiago S. Moreira,
Jan-Marino Ramirez,
Franck Kalume,
Ana C. Takakura
Affiliations
Nicole C. Miranda
Department of Pharmacology, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, SP, São Paulo 05508-000, SP, Brazil; Center for Integrative Brain Research, Seattle Children’s Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA
Luiz M. Oliveira
Center for Integrative Brain Research, Seattle Children’s Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA
Thiago S. Moreira
Department of Physiology and Biophysics, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, SP, São Paulo 05508-000, SP, Brazil
Jan-Marino Ramirez
Center for Integrative Brain Research, Seattle Children’s Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA; Department of Neurological Surgery, University of Washington, 1900 9th Avenue, Seattle, WA 98101, USA; Department of Pediatrics, University of Washington, 1900 9th Avenue, Seattle, WA 98101, USA
Franck Kalume
Center for Integrative Brain Research, Seattle Children’s Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA; Department of Neurological Surgery, University of Washington, 1900 9th Avenue, Seattle, WA 98101, USA
Ana C. Takakura
Department of Pharmacology, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, SP, São Paulo 05508-000, SP, Brazil; Corresponding author
Summary: Parkinson’s disease (PD) is a chronic neurodegenerative disorder affecting the motor system, with non-classic symptoms such as sleep disturbances and respiratory dysfunctions. These issues reflect a complex pathophysiological interaction that severely impacts quality of life. Using a 6-hydroxydopamine (6-OHDA) mouse model of PD, we investigated these connections by analyzing sleep patterns and respiratory parameters during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Our findings revealed altered breathing, including reduced respiratory frequency and increased apneas during both NREM and REM. To address these abnormalities, we employed chemogenetic stimulation of cholinergic neurons in the laterodorsal tegmental nucleus (LDTg), a key region for sleep-wake regulation and respiratory modulation. This intervention normalized respiratory function. These results highlight the critical role of LDTg cholinergic neurons in the coordinating sleep and breathing, suggesting that targeting these neurons could offer a therapeutic strategy for managing PD-related respiratory complications.
