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Respiratory anatomofunctional changes observed in an experimental model of Parkinson Disease


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)

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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)
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.; et al. Purinergic regulation of vascular tone in the retrotrapezoid nucleus is specialized to support the drive to breathe. eLIFE, v. 6, . (16/22069-0, 14/07698-6, 14/22406-1, 15/23376-1)
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, . (15/23376-1, 16/23281-3, 15/18842-3, 14/22406-1)
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, . (13/10573-8, 13/26540-1, 14/22406-1)
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, . (15/11268-0, 12/20398-6, 11/21841-8, 14/22406-1)
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, . (05/56447-7, 14/22406-1)
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, . (15/12827-2, 15/23376-1, 16/22069-0, 11/13462-7, 14/22406-1)
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, . (09/54888-7, 16/23281-3, 15/23376-1, 16/22069-0, 14/22406-1, 13/17251-6)
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, . (13/10573-8, 13/00401-5, 10/09776-3, 14/22406-1)
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, . (11/11934-9, 09/54888-7, 14/22406-1, 13/10573-8)
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, . (14/22406-1, 16/23281-3, 15/23376-1, 15/18842-3, 13/00103-4)
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, . (15/23376-1, 16/23281-3, 15/18842-3, 14/22406-1)
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, . (14/07698-6, 14/22406-1)
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, . (09/54888-7, 14/22406-1, 13/10573-8)

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