Influences of sexual dimorphism, inflammation and sleep on respiratory changes observed in Parkinson’s Disease

• Grant number: 21/09768-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: September 01, 2024
• End date: August 31, 2029
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Carolina Takakura Moreira
• Grantee: Ana Carolina Takakura Moreira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Thiago dos Santos Moreira
• Associated researchers: Bárbara Falquetto ; Fulvio Alexandre Scorza ; Geraldo Lorenzi Filho ; Lauro Casqueiro Vianna ; Maria Aparecida de Oliveira ; Pedro Rodrigues Genta ; Rubens Gisbert Cury ; Thiago dos Santos Moreira
• Associated research grant(s): 24/23629-6 - EMU granted in process 2021/09768-5: sleep recording system in mice, AP.EMU
• Associated scholarship(s): 25/11386-4 - INFLUENCES OF SEXUAL DIMORPHISM ON RESPIRATORY ALTERATIONS OBSERVED IN PARKINSON'S DISEASE, BP.DD

Abstract

Parkinson's disease (PD) is a neurodegenerative disease characterized by the death of dopaminergic neurons in the compact portion of the Substantia Nigra (SNc) which promotes the classic motor symptoms that are related to movement: rest tremor, rigidity, bradykinesia and postural instability. Although these symptoms are responsible for the diagnosis of the disease and are the therapeutic target for it, non-classic symptoms can greatly affect the quality of life of patients with PD. Among these symptoms, changes in breathing and sleep are present. Previous studies from our laboratory examined that in a neurotoxin experimental model of PD, there are changes in regions that control breathing and that are associated with functional respiratory changes. However, there are still many questions regarding the mechanisms that lead to neurodegeneration in these respiratory regions, and little is known about respiratory changes associated with changes in sleep. Thus, the aims of this project are to investigate whether: a) functional and neuroanatomical respiratory changes are also present in female, since all the studies performed until the present moment have used males; b) the mechanisms that lead to neurodegeneration in the respiratory regions depend on an inflammatory process or oxidative stress; c) if the physical activity can be a treatment to prevent respiratory changes observed in an experimental model; d) if there are changes in sleep associated with breathing, both in an experimental model and in patients with PD. We believe in the importance and originality of this study because 1) the proposal has a very novel disease-based rationale. So far, studies of non-classical PD symptoms are the minority, especially related to respiratory changes; 2) Most of the scientists interested in the neural control of breathing study respiratory rhythm generation and central chemoreception but few studies on disease state as PD; 3) The extensive characterization of functional and neuroanatomical respiratory deficits that we have accomplished during the last years provides the key physiological evidence that was needed to bring up the importance of studying respiratory changes in PD; 4) We can study the changes of those regions in vivo, in vitro, and from physiological, anatomical and biomolecular standpoint; 5) We intend to start the translational study by analyzing how breathing can change in patients who have PD. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MIRANDA, NICOLE C.; AQUINO, YASMIN C.; MACEDO, TAINA O.; OLIVEIRA, LUIZ M.; ALBERNAZ-MARIANO, KAIRO A.; MUNHOZ, CAROLINA D.; RAMIREZ, JAN-MARINO; MOREIRA, THIAGO S.; TAKAKURA, ANA C.. Role of substantia Nigra dopaminergic neurons in respiratory modulation and limitations of levodopa in Parkinson's disease. Experimental Neurology, v. 387, p. 13-pg., 2025-02-28. (20/16320-8, 21/05299-0, 21/05647-9, 21/15211-3, 21/09768-5)

MIRANDA, NICOLE C.; OLIVEIRA, LUIZ M.; MOREIRA, THIAGO S.; RAMIREZ, JAN-MARINO; KALUME, FRANCK; TAKAKURA, ANA C.. Sleep-related respiratory disruptions and laterodorsal tegmental nucleus in a mouse model of Parkinson's disease. ISCIENCE, v. 27, n. 11, p. 17-pg., 2024-11-15. (22/07705-9, 21/09768-5, 15/23376-1, 21/05647-9)