Sleep-related respiratory disruptions and laterodorsal tegmental nucleus in a mouse model of Parkinson's disease

Author(s)

Miranda, Nicole C. ; Oliveira, Luiz M. ; Moreira, Thiago S. ; Ramirez, Jan-Marino ; Kalume, Franck ; Takakura, Ana C.

• Document type: Journal article
• Source: ISCIENCE; v. 27, n. 11, p. 17-pg., 2024-11-15.

Abstract

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. (AU)

• FAPESP's process: 22/07705-9 - Respiratory changes associated to sleep observed in Parkinson's Disease
• Grantee: Ana Carolina Takakura Moreira
• Support Opportunities: Scholarships abroad - Research
• FAPESP's process: 21/09768-5 - Influences of sexual dimorphism, inflammation and sleep on respiratory changes observed in Parkinson’s Disease
• Grantee: Ana Carolina Takakura Moreira
• Support Opportunities: Research Projects - Thematic 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: 21/05647-9 - The involvement of pedunculopontine and laterodorsal tegmental nuclei in sleep and respiratory alterations observed in murine model of Parkinsons Disease
• Grantee: Nicole Castro de Souza Miranda
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)