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Analysis of the selective activation of medullary neurons in an experimental model of Parkinson's Disease: a time study of the possible mechanisms for restoration of respiratory function

Grant number: 14/20695-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2015
Effective date (End): April 16, 2019
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Ana Carolina Thomaz Takakura
Grantee:Silvio de Araujo Fernandes Junior
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):17/11165-1 - Respiratory deficit in an experimental model of Parkinson's Disease may be associated with changes in the Phox2b gene at the level of the ventrolateral medulla, BE.EP.DR

Abstract

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder characterized clinically by tremor, rigidity, akinesia (or bradykinesia) and postural instability. The tremor begins asymmetrically and is present at rest, usually involving hands, legs, jaw, lips, affecting the whole face. Pathophysiologically, PD is classified as synocleinopathy associated predominantly with loss of dopaminergic neurons in the substantia nigra (SN), but other brain stem 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. Previous study from our laboratory showed that the induction of PD by injection of 6-hydroxy-dopamine (6-OHDA) in the caudate-putamen (CPu) produced a decrease in the resting respiratory rate and ventilation from day 40 after injury and this change remained until the 60th day after the injury. After 60 days, the immunohistochemical analysis showed a decrease in the number of neurons involved in the neural control of breathing. Objectives: The aims of this project is to correlate the neuroanatomical to respiratory changes found in a PD´s model, we also want to evaluate if the activation of a region involved in the neural control of breathing is able to restore respiratory function in animals subjected to a PD´s model . Methods: Adult male Wistar rats (8 weeks old, 250-280 g) will be used. 6-hydroxy-dopamine (6-OHDA) will be bilaterally injected into the CPu to induce selective cell death of dopaminergic neurons in the SN. Respiratory parameters will be evaluated by whole body plethysmography in different groups of animals in the day before and 30, 40, 50 and 60 days after injection of the toxin. After these periods, the animals will be sacrificed and their brains removed for immunohistochemical processing, evaluating possible changes in neuroanatomical regions responsible for the neural control of breathing. Furthermore, in another experimental group will be assessed if selective or non-selective activation of two regions involved in neural control of breathing (retrotrapezoid nucleus - RTN and pré-Botzinger complex) in animals subjected to the protocol of induction of DP is able to restore respiratory function in these animals. Key Words: Parkinson's disease, retrotrapezoid nucleus, pre-Botzinger complex, breathing. (AU)

Scientific publications
(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)
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.

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