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Effects of pharmacological and non-pharmacological treatments on respiratory changes observed in a murine model of Parkinson's disease

Grant number: 19/01236-4
Support Opportunities:Regular Research Grants
Duration: March 01, 2020 - June 30, 2022
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Ana Carolina Thomaz Takakura
Grantee:Ana Carolina Thomaz Takakura
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Parkinson's disease (PD) is a neurodegenerative disease that affects approximately 1% of the population over 60 years. It is characterized by classic motor symptoms such as bradykinesia, tremors and postural instability. In addition, there are also autonomic non-motor symptoms (constipation, orthostatic hypotension), cognitive and respiratory changes that greatly impair patients' quality of life. Respiratory symptoms, such as obstructive sleep apnea, can lead to the death of PD patients and are present in more advanced stages of the disease. Thus, the understanding of these symptoms in animal models may contribute to the development of more effective or preventive therapies. Animals with damage to the nigrostriatal fibers (PD model) present hypoventilation and a hypercapnia-induced injury response. These functional alterations have a correlation with neuronal and glial changes in specific regions that control breathing, such as the retrotrapezoid nucleus (RTN). Thus, the objective of the present project is to investigate whether the RTN region presents a protein remodeling and associate that to the neuroanatomical changes and investigate if different pharmacological treatments and photostimulation can reverse or reduce these functional respiratory changes. The results of this project may contribute to the development of new therapies for respiratory symptoms of PD and contribute to elucidate the neural substrate of these symptoms. (AU)

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Scientific publications (9)
(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)
MALHEIROS-LIMA, MILENE R.; SILVA, TALITA M.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.. 5 noradrenergic-projecting C1 neurons activate sympathetic and breathing outputs in anaesthetized rat. Experimental Physiology, v. 107, n. 2, . (17/08696-5, 19/01236-4, 15/23376-1)
BATISTA, LUARA A.; CABRAL, LAIS M.; MOREIRA, THIAGO S.; TAKAKURA, ANA C.. nhibition of anandamide hydrolysis does not rescue respiratory abnormalities observed in an animal model of Parkinson's diseas. Experimental Physiology, v. 107, n. 2, . (19/01236-4, 17/18074-1, 15/23376-1)
OLIVEIRA, LUIZ M.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.. Forebrain and Hindbrain Projecting-neurons Target the Post-inspiratory Complex Cholinergic Neurons. Neuroscience, v. 476, p. 102-115, . (15/23376-1, 19/09323-3, 19/01236-4)
SILVA, TALITA M.; BORNIGER, JEREMY C.; ALVES, MICHELE JOANA; CORREA, DIEGO ALZATE; ZHAO, JING; FADDA, PAOLO; TOLAND, AMANDA EWART; TAKAKURA, ANA C.; MOREIRA, THIAGO S.; CZEISLER, CATHERINE M.; et al. Machine learning approaches reveal subtle differences in breathing and sleep fragmentation in Phox2b-derived astrocytes ablated mice. Journal of Neurophysiology, v. 125, n. 4, p. 1164-1179, . (15/23376-1, 18/03994-0, 19/01236-4)
SABINO-CARVALHO, JEANN L.; FALQUETTO, BARBARA; TAKAKURA, ANA C.; VIANNA, LAURO C.. Baroreflex dysfunction in Parkinson's disease: integration of central and peripheral mechanisms. Journal of Neurophysiology, v. 125, n. 4, p. 1425-1439, . (19/00065-1, 19/01236-4)
TAKAKURA, ANA C.; MALHEIROS-LIMA, MILENE R.; MOREIRA, THIAGO S.. Excitatory and inhibitory modulation of parafacial respiratory neurons in the control of active expiration. Respiratory Physiology & Neurobiology, v. 289, . (17/08696-5, 19/01236-4, 15/23376-1)
OLIVEIRA, LUIZ M.; BAERTSCH, NATHAN A.; MOREIRA, THIAGO S.; RAMIREZ, JAN-MARINO; TAKAKURA, ANA C.. Unraveling the Mechanisms Underlying Irregularities in Inspiratory Rhythm Generation in a Mouse Model of Parkinson's Disease. JOURNAL OF NEUROSCIENCE, v. 41, n. 21, p. 4732-4747, . (15/23376-1, 19/09323-3, 19/01236-4)
AQUINO, YASMIN C.; CABRAL, LAIS M.; MIRANDA, NICOLE C.; NACCARATO, MONIQUE C.; FALQUETTO, BARBARA; MOREIRA, THIAGO S.; TAKAKURA, ANA C.. Respiratory disorders of Parkinson's disease. Journal of Neurophysiology, v. 127, n. 1, p. 1-15, . (15/23376-1, 20/16320-8, 19/00065-1, 19/01236-4)
FALQUETTO, BARBARA; THIEME, KARINA; MALTA, MARILIA B.; ROCHA, KARINA C. E.; TUPPY, MARINA; POTJE, SIMONE R.; ANTONIALI, CRISTINA; RODRIGUES, ALICE C.; MUNHOZ, CAROLINA D.; MOREIRA, THIAGO S.; et al. Oxidative stress in the medullary respiratory neurons contributes to respiratory dysfunction in the 6-OHDA model of Parkinson's disease. JOURNAL OF PHYSIOLOGY-LONDON, v. 598, n. 22, . (19/01236-4, 18/05426-0, 19/00065-1, 18/07087-8, 16/03572-3, 15/23376-1, 15/11268-0)

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