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

Abstract

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)

Scientific publications

(19)

(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)

SHI, YINGTANG; SOBRINHO, CLEYTON R.; SOTO-PEREZ, JASEPH; MILLA, BRENDA M.; STORNETTA, DANIEL S.; STORNETTA, RUTH L.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; MOREIRA, THIAGO S.; BAYLISS, DOUGLAS A.. 5-HT7 receptors expressed in the mouse parafacial region are not required for respiratory chemosensitivity. JOURNAL OF PHYSIOLOGY-LONDON, v. 600, n. 11, p. 23-pg., 2022-04-21. (15/23376-1, 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, APR 2021. (15/23376-1, 18/03994-0, 19/01236-4)

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, DEC 2021. (17/08696-5, 19/01236-4, 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, NOV 10 2021. (15/23376-1, 19/09323-3, 19/01236-4)

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, DEC 2021. (19/01236-4, 17/18074-1, 15/23376-1)

TAKAKURA, ANA C.. Botzinger inhibitory neurons and the control of active expiration. JOURNAL OF PHYSIOLOGY-LONDON, v. 599, n. 7, p. 3-pg., 2021-01-19. (19/01236-4)

OLIVEIRA, LUIZ M.; SEVERS, LIZA; MOREIRA, THIAGO S.; RAMIREZ, JAN-MARINO; TAKAKURA, ANA C.. Ampakine CX614 increases respiratory rate in a mouse model of Parkinson's disease. Brain Research, v. 1815, p. 6-pg., 2023-06-13. (19/09323-3, 19/01236-4, 15/23376-1, 17/12266-6)

MIRANDA, NICOLE C.; OLIVEIRA, LUIZ M.; AQUINO, YASMIN C.; MOREIRA, THIAGO S.; TAKAKURA, ANA C.. The Pedunculopontine Tegmental Nucleus is not Important for Breathing Impairments Observed in a Parkinson?s Disease Model. Neuroscience, v. 512, p. 15-pg., 2023-01-27. (19/01236-4, 15/23376-1, 20/16320-8)

DE LA ROSA, TOMAS; CALVO, VIVIAM S.; GONCALVES, VALERIA C.; FERREIRA, CAROLINE B.; CABRAL, LAIS M.; SOUZA, FELIPE DA COSTA; SCERNI, DEBORA A.; SCORZA, FULVIO A.; MOREIRA, THIAGO S.; TAKAKURA, ANA C.. Respiratory deficits in a female rat model of Parkinson's disease. Experimental Physiology, v. 107, n. 11, p. 11-pg., 2022-09-08. (15/23376-1, 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, SEP 2020. (19/01236-4, 18/05426-0, 19/00065-1, 18/07087-8, 16/03572-3, 15/23376-1, 15/11268-0)

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, APR 2021. (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, JUL 2021. (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, MAY 26 2021. (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, JAN 2022. (15/23376-1, 20/16320-8, 19/00065-1, 19/01236-4)

MOREIRA, THIAGO S.; SHI, YINGTANG; SOBRINHO, CLEYTON R.; MILLA, BRENDA M.; SOTA-PEREZ, JASEPH; STORNETTA, DANIEL S.; STORNETTA, RUTH L.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; BAYLISS, DOUGLAS A.. 5-HT7 receptors expressed in the mouse parafacial region are not required for respiratory chemosensitivity. FASEB JOURNAL, v. 36, p. 1-pg., 2022-01-01. (19/01236-4, 15/23376-1)

OLIVEIRA, LUIZ M.; FERNANDES-JUNIOR, SILVIO A.; CABRAL, LAIS M. C.; MIRANDA, NICOLE C. S.; CZEISLER, CATHERINE M.; OTERO, JOSE J.; MOREIRA, THIAGO S.; TAKAKURA, ANA C.. Regulation of blood vessels by ATP in the ventral medullary surface in a rat model of Parkinson's disease. Brain Research Bulletin, v. 187, p. 17-pg., 2022-07-12. (15/23376-1, 17/11165-1, 19/09323-3, 14/20695-6, 19/01236-4)

NASCIMENTO, ANDRE L. F.; MEDEIROS, PAMELA O. S.; PEDRAO, LUIZ F. A. T.; QUEIROZ, VITORIA C.; OLIVEIRA, LUIZ M.; NOVAES, LEONARDO S.; CAETANO, ARIADINY L.; MUNHOZ, CAROLINA D.; TAKAKURA, ANA C.; FALQUETTO, BARBARA. Oxidative Stress Inhibition Via Apocynin Prevents Medullary Respiratory Neurodegeneration and Respiratory Pattern Dysfunction in a 6-Hydroxydopamine Animal Model of Parkinson's Disease. Neuroscience, v. 502, p. 16-pg., 2022-10-15. (15/23376-1, 19/00065-1, 16/03572-3, 19/01236-4)

TAKAKURA, ANA C.. A new neuromodulatory mechanism in the lateral hypothalamus regulating the hypercapnic ventilatory response in conscious rats. Experimental Physiology, v. 107, n. 11, p. 2-pg., 2022-08-27. (19/01236-4)

MOREIRA, THIAGO S.; TAKAKURA, ANA C.; COLOMBARI, EDUARDO. Editorial: Integrative Physiology: Systemic Hypertension and Respiratory-Sympathetic Coupling. FRONTIERS IN PHYSIOLOGY, v. 13, p. 3-pg., 2022-01-26. (15/23376-1, 15/23467-7, 19/01236-4)