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Respiratory anatomofunctional changes observed in an experimental model of Parkinson Disease

Grant number: 14/22406-1
Support type:Regular Research Grants
Duration: August 01, 2015 - July 31, 2017
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Ana Carolina Thomaz Takakura
Grantee:Ana Carolina Thomaz Takakura
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Parkinson´s disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, akinesia (or bradykinesia) and postural instability. Pathophysiologically, PD is classified as synocleinopathy associated predominantly with loss of dopaminergic neurons in the substantia nigra (SN), but other brainstem neurons have been found to degenerate in PD, possibly contributing to the appearance of non-motor abnormalities. In patients with PD is also possible to observe respiratory disabilities whose mechanisms are still unclear. The various respiratory changes observed in PD can be characterized as upper airway obstruction, complications of medicine intake, complications of medication withdrawal and pneumonia. The aims of this project is to study possible mechanisms involved in respiratory problems associated to PD. In this way, we first will study if there are anatomical projections from SN to brainstem nuclei involved in neural control of breathing by anterograde and retrograde tracers injections in those regions. We also want to study the effects in resting breathing and ventilation changes produced by hypercapnia or hypoxia in an experimental model of PD induced by 6-hydroxidopamine (6-OHDA) injection into the striatum. The respiratory parameters will be evaluated for 60 days after 6-OHDA injection. After functional analysis, the animals will be sacrificed, perfused and will have the brains removed for imunohistochemistry treatment to analyze neuroanatomical changes in regions located in the brainstem responsible for neural control of breathing. By the end, we will investigate if selective activation of neurons located in regions involved in neural control of breathing in animals subjected to the protocol of induction of PD is able to restore respiratory function. (AU)

Scientific publications (14)
(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)
ZOCCAL, DANIEL B.; SILVA, JOSIANE N.; BARNETT, WILLIAM H.; LEMES, EDUARDO V.; FALQUETTO, BARBARA; COLOMBARI, EDUARDO; MOLKOV, YAROSLAV I.; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Interaction between the retrotrapezoid nucleus and the parafacial respiratory group to regulate active expiration and sympathetic activity in rats. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, v. 315, n. 5, p. L891-L909, NOV 2018. Web of Science Citations: 5.
LIMA, JULIANA C.; OLIVEIRA, LUIZ M.; BOTELHO, MARINA T.; MOREIRA, THIAGO S.; TAKAKURA, ANA C. The involvement of the pathway connecting the substantia nigra, the periaqueductal gray matter and the retrotrapezoid nucleus in breathing control in a rat model of Parkinson's disease. Experimental Neurology, v. 302, p. 46-56, APR 2018. Web of Science Citations: 6.
MALHEIROS-LIMA, MILENE R.; TOTOLA, LEONARDO T.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. Impaired chemosensory control of breathing after depletion of bulbospinal catecholaminergic neurons in rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 470, n. 2, p. 277-293, FEB 2018. Web of Science Citations: 2.
OLIVEIRA, LUIZ M.; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Raphe Pallidus is Not Important to Central Chemoreception in a Rat Model of Parkinson's Disease. Neuroscience, v. 369, p. 350-362, JAN 15 2018. Web of Science Citations: 4.
SOBRINHO, CLEYTON R.; GONCALVES, CHRISTOPHER M.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; MOREIRA, THIAGO S. Fluorocitrate-mediated depolarization of astrocytes in the retrotrapezoid nucleus stimulates breathing. Journal of Neurophysiology, v. 118, n. 3, p. 1690-1697, SEP 2017. Web of Science Citations: 6.
OLIVEIRA, LUIZ M.; TUPPY, MARINA; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Role of the locus coeruleus catecholaminergic neurons in the chemosensory control of breathing in a Parkinson's disease model. Experimental Neurology, v. 293, p. 172-180, JUL 2017. Web of Science Citations: 14.
MALHEIROS-LIMA, MILENE R.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. DEPLETION OF ROSTRAL VENTROLATERAL MEDULLARY CATECHOLAMINERGIC NEURONS IMPAIRS THE HYPDXIC VENTILATORY RESPONSE IN CONSCIOUS RATS. Neuroscience, v. 351, p. 1-14, MAY 20 2017. Web of Science Citations: 11.
HAWKINS, VIRGINIA E.; TAKAKURA, ANA C.; TRINH, ASHLEY; MALHEIROS-LIMA, MILENE R.; CLEARY, COLIN M.; WENKER, IAN C.; DUBREUIL, TODD; RODRIGUEZ, ELLIOT M.; NELSON, MARK T.; MOREIRA, THIAGO S.; MULKEY, DANIEL K. Purinergic regulation of vascular tone in the retrotrapezoid nucleus is specialized to support the drive to breathe. eLIFE, v. 6, APR 7 2017. Web of Science Citations: 17.
FALQUETTO, BARBARA; TUPPY, MARINA; POTJE, SIMONE R.; MOREIRA, THIAGO S.; ANTONIALI, CRISTINA; TAKAKURA, ANA C. Cardiovascular dysfunction associated with neurodegeneration in an experimental model of Parkinson's disease. Brain Research, v. 1657, p. 156-166, FEB 15 2017. Web of Science Citations: 11.
TOTOLA, LEONARDO T.; TAKAKURA, ANA C.; OLIVEIRA, JOSE ANTONIO C.; GARCIA-CAIRASCO, NORBERTO; MOREIRA, THIAGO S. Impaired central respiratory chemoreflex in an experimental genetic model of epilepsy. JOURNAL OF PHYSIOLOGY-LONDON, v. 595, n. 3, p. 983-999, FEB 2017. Web of Science Citations: 10.
SILVA, TALITA M.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. Acute hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the C1 region. Experimental Neurology, v. 285, n. A, p. 1-11, NOV 2016. Web of Science Citations: 8.
OLIVEIRA, LUIZ M.; MOREIRA, THIAGO S.; KUO, FU-SHAN; MULKEY, DANIEL K.; TAKAKURA, ANA C. alpha(1)- and alpha(2)-adrenergic receptors in the retrotrapezoid nucleus differentially regulate breathing in anesthetized adult rats. Journal of Neurophysiology, v. 116, n. 3, p. 1036-1048, SEP 2016. Web of Science Citations: 10.
MOREIRA, THIAGO S.; TAKAKURA, ANA C.; CZEISLER, CATHERINE; OTERO, JOSE J. Respiratory and autonomic dysfunction in congenital central hypoventilation syndrome. Journal of Neurophysiology, v. 116, n. 2, p. 742-752, AUG 2016. Web of Science Citations: 9.
ALVES, THALES B.; TOTOLA, LEONARDO T.; TAKAKURA, ANA C.; COLOMBARI, EDUARDO; MOREIRA, THIAGO S. GABA mechanisms of the nucleus of the solitary tract regulates the cardiovascular and sympathetic effects of moxonidine. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 194, p. 1-7, JAN 2016. Web of Science Citations: 2.

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