Orexinergic and aminergic mechanisms in respiratory control in an animal model of Parkinsons Disease

• Grant number: 15/18842-3
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2015
• Effective date (End): April 30, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Carolina Thomaz Takakura
• Grantee: Luiz Marcelo Oliveira Santos
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 17/12266-6 - Optogenetic stimulation of pre-Bötzinger complex neurons and the control of breathing in a mice model of Parkinson's disease, BE.EP.DR

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 neurons from aminergic and orexinergic systems project to each other and to RTN using retrograde tracer injections in rats. We will also investigate if the respiratory responses observed in this PD model animal depend on the noradrenergic, serotoninergic and orexinergic neurons integrity by whole body pletismograph. (AU)

Scientific publications

(6)

(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)

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.

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.

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.

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.