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Encephalic regions responsible for neuroplasticity observed in respiratory response induced by hypercapnia in a modelo of Parkinson´s s disease

Grant number: 16/23281-3
Support type:Regular Research Grants
Duration: August 01, 2017 - July 31, 2019
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 progressive loss of dopaminergic neurons in the substantia nigra compacta (SNc). The main motor symptoms are tremor at rest, bradykinesia, classic rigidity and postural instability. However, we can observe non-motor symptoms as neuropsychiatric, sleep and breathing disorders. Neuroanatomical studies show that the number of Phox2b neurons in the retrotrapezoid nucleus (RTN) was reduced in the animal model of PD induced by injection of 6-hydroxydopamine (6-OHDA) into the caudate putamen (CPu) (Tuppy, et al., 2015). In this same model, it was observed that the ventilatory response to hypercapnia was impaired 40 and 50 days after PD induction. However, this response was restored 60 days after PD induction (Tuppy, et al., 2015). These data suggest that any region in place of RTN could assume the function of central chemoreceptor in central nervous system (CNS). The aim of this work is to study if those functional changes observed in this PD model also depend on the aminergic and orexinergic mechanisms, since these systems are also involved in central chemoreception. In that way, we will investigate if the respiratory responses observed in this PD animal model depend on the noradrenergic, serotoninergic and orexinergic neurons integrity by whole body pletismograph and neuroanatomical studies. (AU)

Scientific publications (25)
(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)
MAIA, OCTAVIO A. C.; MALHEIROS-LIMA, MILENE R.; OLIVEIRA, MARIA A.; CASTRO, CLAUDIO L.; MORIYA, HENRIQUE T.; TAVARES-DE-LIMA, WOTHAN; TAKAKURA, ANA C.; MOREIRA, THIAGO S. Pilocarpine-induced status epilepticus reduces chemosensory control of breathing. Brain Research Bulletin, v. 161, p. 98-105, AUG 2020. Web of Science Citations: 1.
FERNANDES-JUNIOR, SILVIO A.; OLIVEIRA, LUIZ M.; CZEISLER, CATHERINE M.; MO, XIAOKUI; ROY, SASHWATI; SOMOGYI, ARPAD; ZHANG, LIEWN; MOREIRA, THIAGO S.; OTERO, JOSE J.; TAKAKURA, ANA C. Stimulation of retrotrapezoid nucleus Phox2b-expressing neurons rescues breathing dysfunction in an experimental Parkinson's disease rat model. Brain Pathology, JUL 2020. Web of Science Citations: 0.
CABRAL, LAIS M.; MOREIRA, THIAGO S.; TAKAKURA, ANA C.; FALQUETTO, BARBARA. Attenuated baroreflex in a Parkinson's disease animal model coincides with impaired activation of non-C1 neurons. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 225, MAY 2020. Web of Science Citations: 1.
SILVA, JOSIANE DO N.; OLIVEIRA, LUIZ M.; SOUZA, FELIPE C.; MOREIRA, THIAGO S.; TAKAKURA, ANA C. GABAergic neurons of the medullary raphe regulate active expiration during hypercapnia. Journal of Neurophysiology, v. 123, n. 5, p. 1933-1943, MAY 2020. Web of Science Citations: 0.
MALHEIROS-LIMA, MILENE R.; SILVA, JOSIANE N.; SOUZA, FELIPE C.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. C1 neurons are part of the circuitry that recruits active expiration in response to the activation of peripheral chemoreceptors. eLIFE, v. 9, JAN 23 2020. Web of Science Citations: 0.
DIAZ, HUGO S.; ANDRADE, DAVID C.; TOLEDO, CAMILO; PEREYRA, V, KATHERIN; SCHWARZ, KARLA G.; DIAZ-JARA, ESTEBAN; LUCERO, CLAUDIA; ARCE-ALVAREZ, ALEXIS; SCHULTZ, HAROLD D.; SILVA, JOSIANE N.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.; MARCUS, NOAH J.; DEL RIO, RODRIGO. Episodic stimulation of central chemoreceptor neurons elicits disordered breathing and autonomic dysfunction in volume overload heart failure. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, v. 318, n. 1, p. L27-L40, JAN 2020. Web of Science Citations: 0.
MALHEIROS-LIMA, MILENE R.; ANTUNES, VAGNER R.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. Hypertension and sympathetic nervous system overactivity rely on the vascular tone of pial vessels of the rostral ventrolateral medulla in spontaneously hypertensive rats. Experimental Physiology, v. 105, n. 1, p. 65-74, JAN 2020. Web of Science Citations: 0.
OLIVEIRA, LUIZ M.; HENRIQUE, ELISANDRA; BUSTELLI, ISABELLA B.; NETTO, NELSON F. C.; MOREIRA, THIAGO S.; TAKAKURA, ANA C.; CAETANO, ARIADINY L. Depletion of hypothalamic hypocretin/orexin neurons correlates with impaired memory in a Parkinson's disease animal model. Experimental Neurology, v. 323, JAN 2020. Web of Science Citations: 0.
LIMA, JANAYNA D.; SOBRINHO, CLEYTON R.; SANTOS, LEONARDO K.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. M4-muscarinic acetylcholine receptor into the pedunculopontine tegmental nucleus mediates respiratory modulation of conscious rats. Respiratory Physiology & Neurobiology, v. 269, NOV 2019. Web of Science Citations: 0.
TOLEDO, CAMILO; ANDRADE, DAVID C.; DIAZ, HUGO S.; PEREYRA, KATHERIN V.; SCHWARZ, KARLA G.; DIAZ-JARA, ESTEBAN; OLIVEIRA, LUIZ M.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.; SCHULTZ, HAROLD D.; MARCUS, NOAH J.; DEL RIO, RODRIGO. Rostral ventrolateral medullary catecholaminergic neurones mediate irregular breathing pattern in volume overload heart failure rats. JOURNAL OF PHYSIOLOGY-LONDON, NOV 2019. Web of Science Citations: 1.
TOTOLA, LEONARDO T.; MALHEIROS-LIMA, MILENE R.; DELFINO-PEREIRA, POLIANNA; DEL VECCHIO, FLAVIO; SOUZA, FELIPE C.; TAKAKURA, ANA C.; GARCIA-CAIRASCO, NORBERTO; MOREIRA, THIAGO S. Amygdala rapid kindling impairs breathing in response to chemoreflex activation. Brain Research, v. 1718, p. 159-168, SEP 1 2019. Web of Science Citations: 1.
SILVA, JOSIANE N.; OLIVEIRA, LUIZ M.; SOUZA, FELIPE C.; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Distinct pathways to the parafacial respiratory group to trigger active expiration in adult rats. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, v. 317, n. 3, p. L402-L413, SEP 2019. Web of Science Citations: 1.
OLIVEIRA, LUIZ M.; OLIVEIRA, MARIA A.; MORIYA, HENRIQUE T.; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Respiratory disturbances in a mouse model of Parkinson's disease. Experimental Physiology, v. 104, n. 5, p. 729-739, MAY 1 2019. Web of Science Citations: 3.
CZEISLER, CATHERINE M.; SILVA, TALITA M.; FAIR, SUMMER R.; LIU, JILLIAN; TUPAL, SRINIVASAN; KAYA, BEHIYE; COWGILL, AARON; MAHAJAN, SALIL; SILVA, PHELIPE E.; WANG, YANGYANG; BLISSETT, ANGELA R.; GOKSEL, MUSTAFA; BORNIGER, JEREMY C.; ZHANG, NING; FERNANDES-JUNIOR, SILVIO A.; CATACUTAN, FAY; ALVES, MICHELE J.; NELSON, RANDY J.; SUNDARESEAN, VISHNU; REKLING, JENS; TAKAKURA, ANA C.; MOREIRA, THIAGO S.; OTERO, JOSE J. The role of PHOX2B-derived astrocytes in chemosensory control of breathing and sleep homeostasis. JOURNAL OF PHYSIOLOGY-LONDON, v. 597, n. 8, p. 2225-2251, APR 15 2019. Web of Science Citations: 4.
LIMA, JANAYNA D.; SOBRINHO, CLEYTON R.; FALQUETTO, BARBARA; SANTOS, LEONARDO K.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; MOREIRA, THIAGO S. Cholinergic neurons in the pedunculopontine tegmental nucleus modulate breathing in rats by direct projections to the retrotrapezoid nucleus. JOURNAL OF PHYSIOLOGY-LONDON, v. 597, n. 7, p. 1919-1934, APR 2019. Web of Science Citations: 2.
ANDRADE, DAVID C.; TOLEDO, CAMILO; DIAZ, HUGO S.; LUCERO, CLAUDIA; ARCE-ALVAREZ, ALEXIS; OLIVEIRA, LUIZ M.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.; SCHULTZ, HAROLD D.; MARCUS, NOAH J.; ALCAYAGA, JULIO; DEL RIO, RODRIGO. Ablation of brainstem C1 neurons improves cardiac function in volume overload heart failure. Clinical Science, v. 133, n. 3, p. 393-405, FEB 14 2019. Web of Science Citations: 4.
MALHEIROS-LIMA, MILENE R.; TOTOLA, LEONARDO T.; LANA, MARLOUS V. G.; STRAUSS, BRYAN E.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. Breathing responses produced by optogenetic stimulation of adrenergic C1 neurons are dependent on the connection with preBotzinger complex in rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 470, n. 11, p. 1659-1672, NOV 2018. Web of Science Citations: 4.
OLIVEIRA, LUIZ M.; FALQUETTO, BARBARA; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Orexinergic neurons are involved in the chemosensory control of breathing during the dark phase in a Parkinson's disease model. Experimental Neurology, v. 309, p. 107-118, NOV 2018. Web of Science Citations: 2.
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.
FERNANDES-JUNIOR, SILVIO A.; CARVALHO, KARIN S.; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Correlation between neuroanatomical and functional respiratory changes observed in an experimental model of Parkinson's disease. Experimental Physiology, v. 103, n. 10, p. 1377-1389, OCT 1 2018. Web of Science Citations: 5.
FALQUETTO, BARBARA; OLIVEIRA, LUIZ M.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; MOREIRA, THIAGO S. Inhibition of the hypercapnic ventilatory response by adenosine in the retrotrapezoid nucleus in awake rats. Neuropharmacology, v. 138, p. 47-56, AUG 2018. Web of Science Citations: 3.
SILVA, TALITA M.; CHAAR, LAIALI J.; SILVA, REINALDO C.; TAKAKURA, ANA C.; CAMARA, NIELS O.; ANTUNES, VAGNER R.; MOREIRA, THIAGO S. Minocycline alters expression of inflammatory markers in autonomic brain areas and ventilatory responses induced by acute hypoxia. Experimental Physiology, v. 103, n. 6, p. 884-895, JUN 1 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.
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.
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.

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